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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 -
Angiogenesis Feb 2019Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor... (Review)
Review
Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.
Topics: Angiogenesis Inhibitors; Animals; Humans; Neovascularization, Pathologic; Pancreatic Neoplasms
PubMed: 30168025
DOI: 10.1007/s10456-018-9645-2 -
Signal Transduction and Targeted Therapy Aug 2023Normal high-density lipoprotein (nHDL) can induce angiogenesis in healthy individuals. However, HDL from patients with coronary artery disease undergoes various...
Normal high-density lipoprotein (nHDL) can induce angiogenesis in healthy individuals. However, HDL from patients with coronary artery disease undergoes various modifications, becomes dysfunctional (dHDL), and loses its ability to promote angiogenesis. Here, we identified a long non-coding RNA, HDRACA, that is involved in the regulation of angiogenesis by HDL. In this study, we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2, which catalyzes the ubiquitination and subsequent degradation of its transcription factor, Kruppel-like factor 5, via sphingosine 1-phosphate (S1P) receptor 1. In contrast, dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA. HDRACA was able to bind to Ras-interacting protein 1 (RAIN) to hinder the interaction between RAIN and vigilin, which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen (PCNA) mRNA, resulting in a decrease in the expression of PCNA and inhibition of angiogenesis. The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis. Taken together, these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis, which nHDL inhibits the expression of HDRACA to induce angiogenesis, and that dHDL is much less effective in inhibiting HDRACA expression, which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.
Topics: Mice; Animals; Humans; Lipoproteins, HDL; Proliferating Cell Nuclear Antigen; RNA, Long Noncoding; Endothelial Cells; Neovascularization, Physiologic
PubMed: 37574469
DOI: 10.1038/s41392-023-01558-6 -
Journal of Clinical Neuroscience :... May 2019Angiogenesis refers to new capillaries that sprout and remold from existing vessels. The mechanism of angiogenesis is very complex. Many factors promote angiogenesis in... (Review)
Review
Angiogenesis refers to new capillaries that sprout and remold from existing vessels. The mechanism of angiogenesis is very complex. Many factors promote angiogenesis in the body, and many factors inhibit angiogenesis. Angiogenesis is closely correlated to oxidative stress. Oxidative stress plays an important role in its positive feedback mechanism. Oxidative stress is defined as the imbalance of the internal oxidation system and antioxidant system, which is correlated to the cause and prognosis of many vascular diseases, and can be used as a biomarker for these diseases. At the same time, good regulation of oxidative stress can promote angiogenesis and tissue repair. Therefore, the present study summarizes the relationship between oxidative stress and angiogenesis, and new progress, and discusses the effect and mechanism of oxidative stress on angiogenesis.
Topics: Animals; Antioxidants; Humans; Neovascularization, Pathologic; Oxidative Stress
PubMed: 30837109
DOI: 10.1016/j.jocn.2019.02.019 -
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 -
Angiogenesis Aug 2020Breast cancer is one of the most common cancers worldwide with a rising incidence, and is the leading cause of cancer-related death among females. Angiogenesis plays an...
Breast cancer is one of the most common cancers worldwide with a rising incidence, and is the leading cause of cancer-related death among females. Angiogenesis plays an important role in breast cancer growth and metastasis. In this study, we identify decylubiquinone (DUb), a coenzyme Q analog, as a promising anti-breast cancer agent through suppressing tumor-induced angiogenesis. We screened a library comprising FDA-approved drugs and found that DUb significantly inhibits blood vessel formation using in vivo chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. DUb was further identified to inhibit angiogenesis in the rat aortic ring and Matrigel plug assay. Moreover, DUb was found to suppress breast cancer growth and metastasis in the MMTV-PyMT transgenic mouse and human xenograft tumor models. To explore whether the anticancer efficacy of DUb was directly corrected with tumor-induced angiogenesis, the MDA-MB-231 breast cancer assay on the CAM was performed. Interestingly, DUb significantly inhibits the angiogenesis of breast cancer on the CAM. Brain angiogenesis inhibitor 1 (BAI1), a member of the G protein-coupled receptor (GPCR) adhesion subfamily, has an important effect on the inhibition of angiogenesis. Further studies demonstrate that DUb suppresses the formation of tubular structures by regulating the reactive oxygen species (ROS)/p53/BAI1 signaling pathway. These results uncover a novel finding that DUb has the potential to be an effective agent for the treatment of breast cancer by inhibiting tumor-induced angiogenesis.
Topics: Animals; Breast Neoplasms; Chick Embryo; Female; Humans; MCF-7 Cells; Neoplasm Metastasis; Neoplasm Proteins; Neovascularization, Pathologic; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Signal Transduction; Tumor Suppressor Protein p53; Ubiquinone
PubMed: 32020421
DOI: 10.1007/s10456-020-09707-z -
Acta Biomaterialia Oct 2021Uncontrolled tumor growth and subsequent distant metastasis are highly dependent on an adequate nutrient supply from tumor blood vessels, which have relatively different... (Review)
Review
Uncontrolled tumor growth and subsequent distant metastasis are highly dependent on an adequate nutrient supply from tumor blood vessels, which have relatively different pathophysiological characteristics from those of normal vasculature. Obviously, strategies targeting tumor vasculature, such as anti-angiogenic drugs and vascular disrupting agents, are attractive methods for cancer therapy. However, the off-target effects and high dose administration of these drug regimens critically restrict their clinical applications. In recent years, nanomedicines focused on tumor vasculature have been shown to be superior to traditional therapeutic methods and do not induce side effects. This review will first highlight the recent development of tumor vasculature-targeting nanomedicines from the following four aspects: 1) angiogenesis-inhibiting nanomedicines (AINs); 2) vasculature-disrupting nanomedicines (VDNs); 3) vasculature infarction nanomedicines (VINs); and 4) vasculature-regulating nanomedicines (VRNs). Furthermore, the design principles, limitations, and future directions are also discussed. STATEMENT OF SIGNIFICANCE: Based on the essential roles of tumor blood vessels, the therapeutic strategies targeting tumor vasculature have exhibited good clinical therapeutic outcomes. However, poor patient adherence to free drug administration limits their clinical usage. Nanomedicines have great potential to overcome the abovementioned obstacle. This review summarizes the tumor-vasculature targeting nanomedicines from four aspects: 1) angiogenesis-inhibiting nanomedicines (AINs); 2) vasculature-disrupting nanomedicines (VDNs); 3) vasculature infarction nanomedicines (VINs); and 4) vasculature regulating nanomedicines (VRNs). In addition, this review provides perspectives on this research field.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Drug Delivery Systems; Humans; Nanomedicine; Neoplasms; Neovascularization, Pathologic
PubMed: 34271167
DOI: 10.1016/j.actbio.2021.07.015 -
Angiogenesis Nov 2023Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These...
Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These different modes of angiogenesis involve, for example, increasing microvasculature density by sprouting of endothelial cells, splitting of vessels to increase vascular surface area by intussusceptive angiogenesis, fusion of capillaries to increase blood flow by coalescent angiogenesis, and the recruitment of non-endothelial cells by vasculogenic mimicry. The recent reporting on coalescent angiogenesis as a new mode of vessel formation warrants a brief overview of angiogenesis mechanisms to provide a more complete picture. The journal Angiogenesis is devoted to the delineation of the different modes and mechanisms that collectively dictate blood vessel formation, inhibition, and function in health and disease.
Topics: Neovascularization, Physiologic; Endothelial Cells; Capillaries; Morphogenesis
PubMed: 37640982
DOI: 10.1007/s10456-023-09895-4 -
Drug Discovery Today Oct 2022Statins inhibit HMG-CoA reductase by competitively inhibiting the active site of the enzyme, thus preventing cholesterol synthesis and reducing the risk of developing... (Review)
Review
Statins inhibit HMG-CoA reductase by competitively inhibiting the active site of the enzyme, thus preventing cholesterol synthesis and reducing the risk of developing cardiovascular disease. Many pleiotropic effects of statins have been demonstrated that can be either related or unrelated to their cholesterol-lowering ability. Among these effects are their proangiogenic and antiangiogenic properties that could offer new therapeutic applications. In this regard, pro- and anti-angiogenic properties of statins have been shown to be dose dependent. Statins also appear to have a variety of non-cardiovascular angiogenic effects in many diseases, some examples being ocular disease, brain disease, cancer, preeclampsia, diabetes and bone disease, which are discussed in this review using reports from in vitro and in vivo investigations.
Topics: Cardiovascular Diseases; Cholesterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neoplasms; Neovascularization, Pathologic
PubMed: 35850434
DOI: 10.1016/j.drudis.2022.07.005