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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 -
Ophthalmology Sep 1995
Review
Topics: Animals; Choroid; Humans; Macular Degeneration; Neovascularization, Pathologic
PubMed: 9097761
DOI: No ID Found -
Drug Resistance Updates : Reviews and... Jun 2012A large number of patients that undergo radiotherapy develop local failure. To improve the efficacy of treatment, there is an increasing interest in combining... (Review)
Review
A large number of patients that undergo radiotherapy develop local failure. To improve the efficacy of treatment, there is an increasing interest in combining radiotherapy with novel targeted therapies. Inhibiting the growth of new tumor blood vessels, i.e. tumor angiogenesis, is such a targeted therapy. Growing tumors induce angiogenesis to ensure an adequate delivery of oxygen and nutrients and several angiostatic drugs have been approved for the treatment of cancer patients. Both pre-clinical and clinical studies have shown that radiotherapy can influence tumor angiogenesis and that angiogenesis inhibition can potentiate the effect of radiotherapy. Therefore, the combination of angiogenesis inhibition and radiotherapy holds a promising future in cancer treatment. However, the radiosensitizing effects of angiogenesis inhibition are transient and recent findings indicate that the effects of irradiation on angiogenesis depend on the dose and treatment schedule. This raises questions regarding the scheduling of both treatment modalities in order to achieve the optimal treatment efficacy with minimal toxicity. In this review the opportunities and pitfalls of combining angiostatic agents with radiotherapy are discussed. The lessons learned from (pre)clinical studies are summarized with an emphasis on scheduling and dosing of the combination therapy. Finally, the opportunities of ongoing clinical studies are discussed and opportunities to improve the combination of angiostatic drugs with radiotherapy are presented.
Topics: Angiogenesis Inhibitors; Animals; Clinical Trials as Topic; Combined Modality Therapy; Humans; Neoplasms; Neovascularization, Pathologic
PubMed: 22561672
DOI: 10.1016/j.drup.2012.04.002 -
Journal of Thoracic Oncology : Official... Jun 2024
Topics: Humans; Angiogenesis Inhibitors; Neovascularization, Pathologic; Angiogenesis
PubMed: 38849162
DOI: 10.1016/j.jtho.2024.02.008 -
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 -
Molecular Aspects of Medicine Feb 2010Angiogenesis is integral to the growth and metastatic spread of tumours, and its targeting is an effective anti-tumour strategy. Currently hundreds of anti-angiogenic... (Review)
Review
Angiogenesis is integral to the growth and metastatic spread of tumours, and its targeting is an effective anti-tumour strategy. Currently hundreds of anti-angiogenic therapeutics exist in varying stages of development, a number of which have recently gained US Food and Drug Administration (FDA) approval for the treatment of various human cancers. One class of anti-angiogenic agents directly inhibit endothelial cell function and induce endothelial cell death so as to prevent their integration into new blood vessels. The mitochondria are the focal point for a variety of pro-apoptotic signals, and this review highlights those anti-angiogenic agents that involve the mitochondria in the execution of endothelial cell death. A brief overview of angiogenesis and the mitochondrial apoptotic pathway is also given.
Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Drug Delivery Systems; Humans; Mitochondria; Neoplasms; Neovascularization, Pathologic
PubMed: 19995570
DOI: 10.1016/j.mam.2009.12.005 -
Pharmacological Research Jan 2022Angiogenesis plays an important role in the growth and metastasis of solid tumors including melanoma. Inhibiting tumor-associated angiogenesis is a tactic in treating...
Angiogenesis plays an important role in the growth and metastasis of solid tumors including melanoma. Inhibiting tumor-associated angiogenesis is a tactic in treating melanoma. Dioscin restrains angiogenesis in colon tumor and has anti-melanoma effects in cell and animal models. In a previous study, we found that dioscin inhibits Src/STAT3 signaling in melanoma cells. Activation of the Src/STAT3 pathway has been shown to promote tumor angiogenesis. This study aimed to determine whether dioscin's anti-melanoma effects is related to inhibiting Src/STAT3 signaling-mediated angiogenesis. In a B16F10 allograft mouse model, we found that dioscin inhibited melanoma growth and angiogenesis. To exclude the impact of tumor growth on angiogenesis, a chicken chorioallantoic membrane (CAM) model was used to verify the anti-angiogenic effect of dioscin. Results showed that dioscin suppressed vessel formation in CAM. To determine if tumor secreted pro-angiogenic cytokines are involved in the anti-angiogenic effect of dioscin, conditioned media from dioscin-treated A375 melanoma cells were used to culture human umbilical vein endothelial cells (HUVECs), and tube formation was monitored. It was observed that the tube formation of HUVECs was inhibited. Mechanistic studies revealed that dioscin inhibited the activation of Src and STAT3, and lowered mRNA and protein levels of STAT3 transcriptionally-regulated genes, in B16F10 melanomas. ELISA assays showed that dioscin decreased the secretion of MMP-2, MMP-9 and VEGF from A375 cells. Over-activation of STAT3 lessened the effects of dioscin in decreasing the secretion of pro-angiogenic cytokines from melanoma cells, and in inhibiting tube formation of HUVECs cultured with conditioned media from melanoma cell cultures. In summary, we for the first time demonstrated that inhibiting Src/STAT3 signaling-mediated angiogenesis is involved in the anti-melanoma effects of dioscin. This study provides further pharmacological groundwork for developing dioscin as an anti-melanoma agent.
Topics: Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Diosgenin; Human Umbilical Vein Endothelial Cells; Humans; Male; Melanoma, Experimental; Mice, Inbred C57BL; Neovascularization, Pathologic; STAT3 Transcription Factor; Tumor Burden; src-Family Kinases; Mice
PubMed: 34822972
DOI: 10.1016/j.phrs.2021.105983 -
Cancer Metastasis Reviews Dec 2012Tumor angiogenesis and metastatic spreading are two highly interconnected phenomena, which contribute to cancer-associated deaths. Thus, the identification of novel... (Review)
Review
Tumor angiogenesis and metastatic spreading are two highly interconnected phenomena, which contribute to cancer-associated deaths. Thus, the identification of novel strategies to target angiogenesis and metastatic spreading is crucial. Polycomb genes are a set of epigenetic effectors, structured in multimeric repressive complexes. EZH2 is the catalytic subunit of Polycomb repressive complex 2 (PRC2), which methylates histone H3 lysine 27, thereby silencing several tumor-suppressor genes. EZH2 is essential for cancer stem cell self-renewal. Interestingly, cancer stem cells are thought to be the seeds of metastatic spreading and are able to differentiate into tumor-associated endothelial cells. Pre-clinical studies showed that EZH2 is able to silence several anti-metastatic genes (e.g., E-cadherin and tissue inhibitors of metalloproteinases), thereby favoring cell invasion and anchorage-independent growth. In addition, EZH2 seems to play a crucial role in the regulation of tumor angiogenesis. High EZH2 expression predicts poor prognosis, high grade, and high stage in several cancer types. Recently, a small molecule inhibitor of PRC2 (DZNeP) demonstrated promising anti-tumor activity, both in vitro and in vivo. Interestingly, DZNeP was able to inhibit cancer cell invasion and tumor angiogenesis in prostate and brain cancers, respectively. At tumor-inhibiting doses, DZNeP is not harmful for non-transformed cells. In the present manuscript, we review current evidence supporting a role of EZH2 in metastatic spreading and tumor angiogenesis. Using Oncomine datasets, we show that DZNeP targets are specifically silenced in some metastatic cancers, and some of them may inhibit angiogenesis. Based on this evidence, we propose the development of EZH2 inhibitors as anti-angiogenic and anti-metastatic therapy.
Topics: Animals; Disease Progression; Enhancer of Zeste Homolog 2 Protein; Humans; Neoplasm Invasiveness; Neoplasms; Neovascularization, Pathologic; Polycomb Repressive Complex 2
PubMed: 22711031
DOI: 10.1007/s10555-012-9387-3 -
Progress in Retinal and Eye Research Nov 2003Retinal angiogenesis and choroidal angiogenesis are major causes of vision loss, and the pathogenesis of this angiogenesis process is still uncertain. However, several... (Review)
Review
Retinal angiogenesis and choroidal angiogenesis are major causes of vision loss, and the pathogenesis of this angiogenesis process is still uncertain. However, several key steps of the angiogenic cascade have been elucidated. In retinal angiogenesis, hypoxia is the initial stimulus that causes up regulation of growth factors, integrins and proteinases, which result in endothelial cell proliferation and migration that are critical steps in this process. Once the endothelial tube is formed from the existing blood vessels, maturation starts with recruitment of mural cell precursors and formation of the basement membrane. Normally, there is a tight balance between angiogenic factors and endogenous angiogenesis inhibitors that help to keep the angiogenic process under control. Although the steps of choroidal angiogenesis seem to be similar to those of retinal angiogenesis, there are some major differences between these two processes. Several anti-angiogenic approaches are being developed in animal models to prevent ocular angiogenesis by blocking the key steps of the angiogenic cascade. Based on these pre-clinical studies, several anti-angiogenic clinical trials are ongoing in patients with diabetic retinopathy and age-related macular degeneration. This review discusses the pathogenesis of retinal and choroidal angiogenesis, and alternative pharmacological approaches to inhibit angiogenesis in ocular diseases.
Topics: Animals; Choroid; Humans; Neovascularization, Pathologic; Retinal Vessels
PubMed: 14575722
DOI: 10.1016/j.preteyeres.2003.08.001 -
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