Browsing by Subject "angiogenesis"
Now showing 1 - 6 of 6
- Results Per Page
- Sort Options
Item EGCG and Its Role in Prostate Cancer Angiogenesis(2005-05-01) Thomas, Rusha; Porunelloor Mathew; Ming-Chi Wu; Dan DimitrijevichThomas, Rusha, EGCG and its role in prostate cancer angiogenesis. Master of Science (Biochemistry and Molecular Biology), May 2005, 47 pages, 14 illustrations, reference list, 44 titles. Hypoxia inducible factor-1 (HIF-1)-mediated upregulation of vascular endothelial growth factor (VEGF) has been implicated in angiogenesis associated with malignancies. HIF-1 consists of a constitutively expressed HIF-1β subunit, and a hypoxia-inducible HIF-1α subunit. Hypoxic induction of HIF-1α correlates with increased transcriptional activation of its downstream target genes, including VEGF. Epidemiologic and laboratory studies indicate that green tea has cancer preventive activity which has been attributed to its polyphenol components, the major one being epigallocatechin gallate (EGCG). This study investigated the effect of EGCG on normoxic VEGF expression in PC-3ML human prostate cancer cells. In contrast to previous studies where EGCG inhibited VEGF expression in breast and colon cancer cell lines, our results demonstrated that EGCG has the ability to upregulate HIF-1α transcription factor via inhibition of prolyl hydroxylation and subsequent von Hippel-Lindau protein interaction. HIF-1α upregulation by EGCG led to increased VEGF promoter activity and protein expression.Item Enhanced Angiogenesis in HUVECs Preconditioned with Media from Adipocytes Differentiated from Lipedema Adipose Stem Cells In Vitro(MDPI, 2023-09-09) Al-Ghadban, Sara; Walczak, Samantha G.; Isern, Spencer U.; Martin, Elizabeth C.; Herbst, Karen L.; Bunnell, Bruce A.Lipedema is a connective tissue disorder characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. This project aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). The impacts on the expression levels of multiple endothelial and angiogenic markers [CD31, von Willebrand Factor (vWF), angiopoietin 2 (ANG2), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMPs), NOTCH and its ligands] in HUVECs were investigated. The data demonstrate an increased expression of CD31 and ANG2 at both the gene and protein levels in HUVECs treated with AQL CM in 2D monolayer and 3D cultures compared to untreated cells. Furthermore, the expression of the vWF, NOTCH 4, and DELTA-4 genes decreased. In contrast, increased VEGF, MMP9, and HGF gene expression was detected in HUVECs treated with AQL CM cultured in a 2D monolayer. In addition, the results of a tube formation assay indicate that the number of formed tubes increased in lipedema-treated HUVECs cultured in a 2D monolayer. Together, the data indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.Item Limb Ischemic Conditioning Improved Cognitive Deficits via eNOS-Dependent Augmentation of Angiogenesis after Chronic Cerebral Hypoperfusion in Rats(JKL International, 2018-10-01) Ren, Changhong; Li, Ning; Li, Sijie; Han, Rongrong; Huang, Qingjian; Hu, Jiangnan; Jin, Kunlin; Ji, XunmingIntracranial and extracranial arterial stenosis, the primary cause of chronic cerebral hypoperfusion (CCH), is a critical reason for the pathogenesis of vascular dementia and Alzheimer's disease characterized by cognitive impairments. Our previous study demonstrated that limb remote ischemic conditioning (LRIC) improved cerebral perfusion in intracranial arterial stenosis patients. The current study aimed to test whether LRIC promotes angiogenesis and increases phosphorylated endothelial nitric oxide synthase (p-eNOS) activity in CCH rat model. Adult male Sprague-Dawley rats were randomly assigned to three different groups: sham group, bilateral carotid artery occlusion (2VO) group and 2VO+LRIC group. Cerebral Blood Flow (CBF) was measured with laser speckle contrast imager at 4 weeks. Cognitive testing was performed at four and six weeks after 2VO surgery. We demonstrated that LRIC treatment increased cerebral perfusion and improved the CCH induced spatial learning and memory impairment. Immunohistochemistry confirmed that LRIC prevented cell death in the CA1 region, and increased the number of vessels and angiogenesis in the hippocampus after 2VO. Western blot analysis shows that LRIC therapy significantly increased p-eNOS expression in the hippocampus when compared with 2VO rats. Moreover, eNOS inhibitor reduced the effect of LRIC on angiogenesis in the hippocampus and spatial learning and memory function. Our data suggested that LRIC promoted angiogenesis, which is mediated, in part, by eNOS/NO.Item Role of Exosomal Annexin A2 in Angiogenesis and Breast Cancer Metastasis(2015-05-01) Maji, Sayantan; Vishwanatha, Jamboor K.; Clark, Abbot F.; Gryczynski, IgnacyEarly detection of cancer using circulating biomarkers is a realistic possibility with the discovery of exosomes. Cells under both physiological and pathological conditions secrete a wide array of membranous vesicles containing specific protein and RNA signatures. Exosomes, which are 40-100 nm in size, comprise a major portion of these vesicles. Exosomes play important roles in promoting tumor progression and metastasis, but the mechanisms by which they act are not yet understood. Annexin A2 (AnxA2) is a 36 kDa calcium dependent phospholipid-binding protein up-regulated in many cancer types that promotes tumorigenesis and angiogenesis. Although AnxA2 is highly expressed in exosomes, its function has never been characterized. In this study first we characterized exosomal AnxA2 (exo-AnxA2) expression in a breast cancer progression model. We found that exo-AnxA2 expression is significantly higher in malignant cells than normal and premetastatic cells. Next we explored the correlation and functionality of exo-AnxA2 in angiogenesis and breast cancer metastasis. In vitro and in vivo angiogenesis studies showed that exo-AnxA2 is an important mediator of angiogenesis and targeting the N-terminus of AnxA2 with a competitive hexapeptide greatly reduce the angiogenic effects induced by exo-AnxA2. To study the role of exo-AnxA2 in breast cancer metastasis we used MDA-MB-231 breast cancer cell line and its organ specific metastatic variants MDA-MB-831 (brain metastatic) and MDA-MB-4175 (lung metastatic) breast cancer cells. By using exosome priming in a mouse model, we show that priming with exosomes from metastatic breast cancer cells creates a favorable microenvironment for metastasis, and priming with exo-AnxA2 depleted exosomes leads to reduction of brain as well as lung metastasis. Detailed analysis of the signaling pathways revealed that p38MAPK/NF-κB and STAT3 pathways were up-regulated in the cancer exosomes primed animals than AnxA2 depleted exosome primed animals. These data demonstrate an important role for exo-AnxA2 in breast cancer pathogenesis. Finally, to validate whether exo-AnxA2 can be developed as s potential biomarker, we screened 50 breast cancer serum samples and 50 age matched control samples. Clinical analysis of the serum samples revealed that exo-AnxA2 is over expressed in breast cancer serum samples compared to normal samples. Detailed analysis of the exo-AnxA2 levels among breast cancer subtypes showed that more aggressive breast cancer subtype TNBC has higher exo-AnxA2 levels than HER2+ samples. In summary, our data suggest that exo-AnxA2 plays a major role in promoting angiogenesis and breast cancer metastasis. Further, breast cancer serum samples have higher exo-AnxA2 expression than control samples. Thus, exo-AnxA2 can be a potential diagnostic and prognostic marker in breast cancer patients to detect and monitor metastasis.Item Salivary Exosomes in Health and Disease: Future Prospects in the Eye(MDPI, 2023-04-14) Liu, Angela; Hefley, Brenna; Escandon, Paulina; Nicholas, Sarah E.; Karamichos, DimitriosExosomes are a group of vesicles that package and transport DNA, RNA, proteins, and lipids to recipient cells. They can be derived from blood, saliva, urine, and/or other biological tissues. Their impact on several diseases, such as neurodegenerative, autoimmune, and ocular diseases, have been reported, but not fully unraveled. The exosomes that are derived from saliva are less studied, but offer significant advantages over exosomes from other sources, due to their accessibility and ease of collection. Thus, their role in the pathophysiology of diseases is largely unknown. In the context of ocular diseases, salivary exosomes have been under-utilized, thus creating an enormous gap in the literature. The current review discusses the state of exosomes research on systemic and ocular diseases and highlights the role and potential of salivary exosomes as future ocular therapeutic vehicles.Item Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal(MDPI, 2023-01-22) Kumar, Suneel; Mathew, Stephen O.; Aharwal, Ravindra P.; Tulli, Hardeep S.; Mohan, Chakrabhavi D.; Sethi, Gautam; Ahn, Kwang-Seok; Webber, Kassidy; Sandhu, Sardul S.; Bishayee, AnupamCancer represents the second most deadly disease and one of the most important public health concerns worldwide. Surgery, chemotherapy, radiation therapy, and immune therapy are the major types of treatment strategies that have been implemented in cancer treatment. Unfortunately, these treatment options suffer from major limitations, such as drug-resistance and adverse effects, which may eventually result in disease recurrence. Many phytochemicals have been investigated for their antitumor efficacy in preclinical models and clinical studies to discover newer therapeutic agents with fewer adverse effects. Withaferin A, a natural bioactive molecule isolated from the Indian medicinal plant Withania somnifera (L.) Dunal, has been reported to impart anticancer activities against various cancer cell lines and preclinical cancer models by modulating the expression and activity of different oncogenic proteins. In this article, we have comprehensively discussed the biosynthesis of withaferin A as well as its antineoplastic activities and mode-of-action in in vitro and in vivo settings. We have also reviewed the effect of withaferin A on the expression of miRNAs, its combinational effect with other cytotoxic agents, withaferin A-based formulations, safety and toxicity profiles, and its clinical potential.