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Angiogenesis Nov 2022While inhibiting pathological angiogenesis has been long associated with the field of oncology, recent advances in angiogenesis research have impacted the progress of...
While inhibiting pathological angiogenesis has been long associated with the field of oncology, recent advances in angiogenesis research have impacted the progress of disease treatment for additional non-malignant diseases or chronic conditions in the fields of ophthalmology, cardiology, and gynecology. Moreover, stimulators of angiogenesis find application in ischemic diseases, while inhibitors of angiogenesis are being used to limit blood vessel formation, but in judicious ways that modify or "reprogram" the vasculature as a reinforcement for immunotherapy. We have noticed an increasing impact, as evidenced by increases in the total number of citations, in the literature surrounding the angiogenesis field suggesting that targeting angiogenesis per se is well established as a tractable approach for therapy in diverse conditions.
Topics: Angiogenesis Inhibitors; Humans; Immunotherapy; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 35881257
DOI: 10.1007/s10456-022-09849-2 -
Molecular Neurobiology May 2020Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on... (Review)
Review
Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on the formation of new blood vessels. Angiogenesis is a complex process involving proliferation, migration, and differentiation of vascular endothelial cells (ECs) under the stimulation of specific signals. It is controlled by the balance between its promoting and inhibiting factors. Various angiogenic factors and genes have been identified that stimulate glioma angiogenesis. Therefore, attention has been directed to anti-angiogenesis therapy in which glioma proliferation is inhibited by inhibiting the formation of new tumor vessels using angiogenesis inhibitory factors and drugs. Here, in this review, we highlight and summarize the various molecular mediators that regulate GBM angiogenesis with focus on recent clinical research on the potential of exploiting angiogenic pathways as a strategy in the treatment of GBM patients.
Topics: Adult; Angiogenesis Inhibitors; Angiogenic Proteins; Antineoplastic Agents; Brain Neoplasms; Cell Differentiation; Cell Hypoxia; Clinical Trials as Topic; Glioblastoma; Humans; Intercellular Signaling Peptides and Proteins; Matrix Metalloproteinases; Molecular Targeted Therapy; Neoplasm Proteins; Neoplastic Stem Cells; Neovascularization, Pathologic; Neovascularization, Physiologic; Tumor Microenvironment; Vascular Endothelial Growth Factor A
PubMed: 32152825
DOI: 10.1007/s12035-020-01892-8 -
Journal of Experimental & Clinical... Oct 2018Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding...
BACKGROUND
Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding its anti-tumor mechanism still remain unclear.
METHODS
Cell viability and proliferation were measured by CCK8 and CFSE dilution assay. The localization of p50/p65 or cytochrome c was determined using confocal immunofluorescence. Streptavidin-agarose pulldown or ChIP assays were used to detect the binding of multiple transactivators to COX-2 promoter. The promoter activity was examined by a dual-Luciferase reporter assay. The functions of Andro on COX-2-mediated angiogenesis were also investigated using human HUVEC cells through tube formation and spheroids sprouting assay. The in vivo anti-tumor efficacy of Andro was analyzed in xenografts nude mice.
RESULTS
The results indicated that Andro could significantly inhibit the proliferation of human breast cancers, and suppress COX-2 expression at both protein and mRNA levels. Furthermore, Andro could dose-dependently inhibit COX-2-mediated angiogenesis in human endothelial cells. We have also found that Andro significantly promoted the activation of cytochrome c and activated caspase-dependent apoptotic signaling pathway. Our further explorations demonstrated that Andro inhibited the binding of the transactivators CREB2, C-Fos and NF-κB and blocked the recruitment of coactivator p300 to COX-2 promoter. Moreover, Andro could effectively inhibit the activity of p300 histone acetyltransferase (HAT), thereby attenuating the p300-mediated acetylation of NF-κB. Besides, Andro could also dramatically inhibit the migration, invasion and tubulogenesis of HUVECs in vitro. In addition, Andro also exhibited effective anti-tumor efficacy as well as angiogenesis inhibition in vivo.
CONCLUSION
In current study, we explore the potential effects of Andro in suppressing breast cancer growth and tumor angiogenesis, as well as the precise mechanisms. This work demonstrated the potential anti-cancer effects of Andro, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Diterpenes; E1A-Associated p300 Protein; Female; Humans; Mice; Mice, Nude; Neovascularization, Pathologic; Signal Transduction; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays
PubMed: 30314513
DOI: 10.1186/s13046-018-0926-9 -
Chemical Society Reviews Jul 2020Angiogenesis plays a critical role within the human body, from the early stages of life (i.e., embryonic development) to life-threatening diseases (e.g., cancer, heart... (Review)
Review
Angiogenesis plays a critical role within the human body, from the early stages of life (i.e., embryonic development) to life-threatening diseases (e.g., cancer, heart attack, stroke, wound healing). Many pharmaceutical companies have expended huge efforts on both stimulation and inhibition of angiogenesis. During the last decade, the nanotechnology revolution has made a great impact in medicine, and regulatory approvals are starting to be achieved for nanomedicines to treat a wide range of diseases. Angiogenesis therapies involve the inhibition of angiogenesis in oncology and ophthalmology, and stimulation of angiogenesis in wound healing and tissue engineering. This review aims to summarize nanotechnology-based strategies that have been explored in the broad area of angiogenesis. Lipid-based, carbon-based and polymeric nanoparticles, and a wide range of inorganic and metallic nanoparticles are covered in detail. Theranostic and imaging approaches can be facilitated by nanoparticles. Many preparations have been reported to have a bimodal effect where they stimulate angiogenesis at low dose and inhibit it at higher doses.
Topics: Animals; Carbon; Humans; Lipids; Nanomedicine; Nanoparticles; Nanotechnology; Neovascularization, Pathologic; Polymers
PubMed: 32538379
DOI: 10.1039/c8cs01021h -
International Journal of Molecular... Apr 2022A co-culture assay with human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs) was used to study whether selected angiogenesis...
A co-culture assay with human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs) was used to study whether selected angiogenesis inhibitors were able to inhibit differentiation and network formation of HUVECs in vitro. The effect of the inhibitors was determined by the morphology and the calculated percentage area covered by HUVECs. Neutralizing VEGF with avastin and polyclonal goat anti-VEGF antibody and inhibiting VEGFR2 with sorafenib and vatalanib resulted in the formation of HUVEC clusters of variable sizes as a result of inhibited EC differentiation. Furthermore, numerous inhibitors of the VEGF signaling pathways were tested for their effect on the growth and differentiation of HUVECs. The effects of these inhibitors did not reveal a cluster morphology, either individually or when combined to block VEGFR2 downstream pathways. Only the addition of -methyl--bromolevamisole revealed a similar morphology as when targeting VEGF and VEGFR2, meaning it may have an inhibitory influence directly on VEGFR signaling. Additionally, several nuclear receptor ligands and miscellaneous compounds that might affect EC growth and differentiation were tested, but only dexamethasone gave rise to cluster formation similarly to VEGF-neutralizing compounds. These results point to a link between angiogenesis, HUVEC differentiation and glucocorticoid receptor activation.
Topics: Angiogenesis Inhibitors; Cell Movement; Cell Proliferation; Human Umbilical Vein Endothelial Cells; Humans; Neovascularization, Physiologic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
PubMed: 35457095
DOI: 10.3390/ijms23084277 -
The Journal of Investigative... Dec 2000In order to grow beyond minimal size and to metastasize, tumors need to induce the growth of new blood vessels (angiogenesis). Whereas in normal tissues, vascular... (Review)
Review
In order to grow beyond minimal size and to metastasize, tumors need to induce the growth of new blood vessels (angiogenesis). Whereas in normal tissues, vascular quiescence is maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli, tumor angiogenesis is induced by increased secretion of angiogenic factors and/or by downregulation of angiogenesis inhibitors. Recent evidence suggests vascular endothelial growth factor (VEGF) as the major tumor angiogenesis factor, promoting tumor growth, invasion, and metastasis. Conversely, blocking of VEGF function inhibits angiogenesis and suppresses tumor growth in vivo. Newly identified members of the VEGF family of angiogenesis factors include placental growth factor, VEGF-B, VEGF-C, and VEGF-D, and show overlapping binding patterns to specific endothelial cell receptors. VEGF-C appears to play a major role as a lymphangiogenesis factor and as a growth factor for Kaposi's sarcoma. In contrast, endogenous inhibitors prevent blood vessel growth in normal tissues. In particular, thrombospondin-1 (TSP-1) and TSP-2 are expressed in normal skin and, when introduced into squamous cell carcinomas, potently inhibit malignant tumor growth via inhibition of tumor angiogenesis.
Topics: Animals; Endothelial Growth Factors; Humans; Lymphokines; Neovascularization, Pathologic; Skin Neoplasms; Thrombospondin 1; Thrombospondins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 11147670
DOI: 10.1046/j.1087-0024.2000.00003.x -
The Israel Medical Association Journal... May 2019Angiogenesis is the outgrowth of new blood vessels from existing ones and is an early occurrence in inflamed joint tissue. It is governed by a tightly controlled balance... (Review)
Review
Angiogenesis is the outgrowth of new blood vessels from existing ones and is an early occurrence in inflamed joint tissue. It is governed by a tightly controlled balance of pro- and anti-angiogenic stimuli, which promote or inhibit generation and proliferation of new endothelial cells, vascular morphogenesis, and vessel remodeling. At the beginning, capillary formation is crucial in maintaining the supply of various nutrients as well as oxygen to the inflamed tissue. Local and systemic expression of angiogenic factors may indicate a constant remodeling of synovial vasculature. Redox signaling is closely related to angiogenesis and can alter angiogenic responses of synovial cells. In this review we discuss key issues about the endothelial pathology in inflammatory arthritis followed by a review of angiogenic processes and main angiogenic mediators. We discuss the hypoxia-vascular endothelial growth factor (VEGF)-Ang/Tie2 system and its related therapeutic implications in detail with further review of various mediator protein targets and intracellular regulatory pathway targets with their current and potential future role in preclinical or clinical setting whilst ameliorating inflammation.
Topics: Angiogenic Proteins; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Humans; Neovascularization, Pathologic; Synovial Membrane; Vascular Remodeling
PubMed: 31140228
DOI: No ID Found -
Stem Cell Research & Therapy Nov 2020Rotator cuff tears (RCTs) often require reconstructive surgery. Tendon-bone healing is critical for the outcome of rotator cuff reconstruction, but the process of...
BACKGROUND
Rotator cuff tears (RCTs) often require reconstructive surgery. Tendon-bone healing is critical for the outcome of rotator cuff reconstruction, but the process of tendon-bone healing is complex and difficult. Mesenchymal stem cells (MSCs) are considered to be an effective method to promote tendon-bone healing. MSCs have strong paracrine, anti-inflammatory, immunoregulatory, and angiogenic potential. Recent studies have shown that MSCs achieve many regulatory functions through exosomes. The purpose of this study was to explore the role of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) in tendon-bone healing.
METHODS
Our study found that BMSC-Exos promote the proliferation, migration, and angiogenic tube formation of human umbilical vein endothelial cells (HUVECs). The mechanism by which BMSC-Exos achieve this may be through the regulation of the angiogenic signaling pathway. In addition, BMSC-Exos can inhibit the polarization of M1 macrophages and inhibit the secretion of proinflammatory factors by M1 macrophages. After rotator cuff reconstruction in rats, BMSC-Exos were injected into the tail vein to analyze their effect on the rotator cuff tendon-bone interface healing.
RESULTS
It was confirmed that BMSC-Exos increased the breaking load and stiffness of the rotator cuff after reconstruction in rats, induced angiogenesis around the rotator cuff endpoint, and promoted growth of the tendon-bone interface.
CONCLUSION
BMSC-Exos promote tendon-bone healing after rotator cuff reconstruction in rats by promoting angiogenesis and inhibiting inflammation.
Topics: Animals; Exosomes; Macrophages; Mesenchymal Stem Cells; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Rotator Cuff; Tendons
PubMed: 33239091
DOI: 10.1186/s13287-020-02005-x -
International Journal of Molecular... Dec 2016Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable... (Review)
Review
Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the . In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings. Further on, given the paramount role of integrins in cancer, we will present novel strategies for integrin inhibition that are starting to emerge, promising a hopeful future regarding cancer treatment.
Topics: Animals; Apoptosis; Humans; Integrins; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 27929432
DOI: 10.3390/ijms17122037 -
Human Vaccines Sep 2011Tumors stimulate angiogenesis to meet increasing nutrient and oxygen demands. In addition to their role in vascular remodeling, pro-angiogenic cytokines and effector...
Tumors stimulate angiogenesis to meet increasing nutrient and oxygen demands. In addition to their role in vascular remodeling, pro-angiogenic cytokines and effector cells contribute to an immune-inhibitory environment associated with advanced malignancies. Despite the critical role of angiogenesis in tumor growth and dissemination, most anti-angiogenic cancer therapies have had only limited success selectively targeting one of the many factors implicated in this process. Similarly, the effectiveness of tumor immunotherapies has been limited by tumor-mediated escape mechanisms and immune suppression. By combining the two strategies, however, anti-angiogenic immunotherapy offers the possibility to more robustly inhibit tumor angiogenesis and simultaneously impact the immune-inhibitory effects of the pro-angiogenic tumor milieu. These potential synergies make the combination of immunotherapy and anti-angiogenic treatment a promising avenue for future research.
Topics: Angiogenesis Inhibitors; Animals; Cancer Vaccines; Humans; Immunotherapy; Neoplasms; Neovascularization, Pathologic
PubMed: 21860259
DOI: 10.4161/hv.7.9.16407