Thrmobospondin-1 is the multifunctional protein that modulates endothelial cell and tumor cell behavior via several cell surface receptors and inhibits angiogenesis. In vitro, thrombospondin-1 alters adhesion, proliferation, motility, and survival of endothelial and cancer cells. Studies have confirmed that increased TSP-1 expression suppresses growth or metastasis of some tumors and inhibits angiogenesis. In the past three decades, inhibitors of angiogenesis have been developed as regulators target the vascular endothelial growth factor (VEGF) signaling pathway and small molecule tyrosine kinase inhibitors have been clinically approved. TSP-1 has several functional domain structures and inhibits tumor angiogenesis by engaging receptors CD36 and CD47. TSP-1 binding to CD47 dissociates it from VEGFR2, inhibiting downstream AKT activation and functional responses of endothelial cells to VEGF. Recently, macrophage phagocytosis and cytotoxic T-cell induction of tumor cells mediated by CD47-specific blocking antibodies have been proposed. These findings provide a new therapeutic paradigm for elinination of cancer cells and inhibition of angiogenesis of tumor by TSP-1.
Antibodies, Blocking ; Endothelial Cells ; Macrophages ; Neoplasm Metastasis ; Phagocytosis ; Protein-Tyrosine Kinases ; Receptors, Cell Surface ; T-Lymphocytes ; Thrombospondin 1 ; Vascular Endothelial Growth Factor A

Angiogenesis plays a fundamental role in development of circulation system, reorganization of reproductive system, wound healing. Pathological angiogenesis is deeply involved in a variety of diseases, particularly solid tumor growth and metastasis. However, it is not easy to study the mechanism of angiogenesis because endothelial cells proceed complex differentiation by interaction with extracellular matrix proteins and growth factors. However, human umbilical vein endothelial cells (HUVEC) form polygonal networks of capillary-like tubes in 3D Matrigel cultures. Differentiation of endothelial cells will be observed accurately by application of videomicroscopy. Thrombospondin-1 is secreted by a wide variety of cells including endothelial cells and is incorporated into their matrix. Thrombospondin-1 can modulate differentiation of endothelial cells by increasing cell-cell interactions as well as cell-substrate interactions. The current study was undertaken to determine which mechanism is involved in inhibition of angiogenesis by Thrombospondin-1. They was secreted from HUVEC during the process of angiogenesis in 3D Matrigel culture. When applied to endothelial cells attachment to the surface of Matrigel was not decreased, but spreading was decreased. In addition, bigger clusters was formed by enhancement of cell to cell binding by Thrombospondin-1. They inhibit cord and tube formation of HUVEC by inhibition of migration. These results suggest that Thrombospondin-1 inhibits angiogenesis by blocking differentiation of endothelial cells to motile phenotype in 3D Matrigel culture.
Cell Culture Techniques* ; Endothelial Cells* ; Extracellular Matrix Proteins ; Human Umbilical Vein Endothelial Cells ; Intercellular Signaling Peptides and Proteins ; Microscopy, Video ; Neoplasm Metastasis ; Neovascularization, Pathologic ; Phenotype ; Wound Healing

Purpose: This study aimed to identify the effects of emotional intelligence and self-leadership on job satisfaction among physician assistant nurses. Methods: The participants were 146 physician assistant nurses working at two university hospitals. Data were collected from August 1-September 31, 2020 and analyzed through t-test, ANOVA, Scheffé ́ test, Pearson correlation, and hierarchical regression analysis using SPSS/WIN version 26.0. Results: Factors affecting job satisfaction were self-leadership (β=.30, p=.003), “less than 1 year of experience as a physician assistant nurse” (β=.27, p=.025), and emotional intelligence (β=.25, p=.007), and the explanatory power was 34.4% (F=6.03, p<.001). Conclusion Our study shows that self-leadership and emotional intelligence play a significant role in the job satisfaction of physician assistant nurses; thus, strengthening these two factors is crucial to improve the nurses’ job satisfaction. The results of this study may serve as basic data for the development of strategies to enhance job satisfaction among physician assistant nurses.

Angiogenesis is the fundamental biological phenomenon in the development of vertebrates and various pathophysiological process such as cancer, inflammation and wound healing. Thrombospondin-1 is a well-known anti-angiogenic molecule which is distributed in the extracellular matrix of various tissues. The second and third type I repeats of human TSP-1 have inhibitory effects on endothelial cell migration and induce angiogenesis inhibition. However the role of the first type I repeat was not elucidated. In addition, the first type I repeat of bovine TSP-1 has CSVTCG amino acid sequence which is known to have anti-angiogenic activity. In the present study, we compared the inhibition of angiogenesis to investigate the role of the first type I repeat of the human and bovine TSP-1. Matrigel was mixed with or without TSR-1 peptides and then injected into C57BL/6J mice. We compared angiogenesis inhibition activity by hemoglobin assay, microvessel density and optical density value after 7 days. Furthermore, inhibition of angiogenesis was confirmed on CAM assay by TSR-1 peptides. For in vitro angiogenesis assay, TSR-1 peptides were treated on the proliferation, migration, and tube formation assay of HUVEC. Apoptosis effect of TSR-1 peptides was confirmed by apoptosis assay kit and flow cytometry. Bovine and human TSR-1 peptides blocked neovascularization in in vivo Matrigel plug assay and CAM assay at 10 microM. Bovine TSR-1 peptides have shown stronger angiogenesis inhibition in bFGF-induced angiogenesis than human TSR-1 and CSVTCG peptides. However, all of TSR-1 peptides inhibit migration and tube formation of HUVEC in in vitro. Furthermore, these peptides also induced apoptosis of HUVEC. These results suggest that TSR-1 peptides of bovine and human TSP-1 have angiogenesis inhibition activity.
Amino Acid Sequence ; Animals ; Apoptosis ; Biological Phenomena ; Endothelial Cells ; Extracellular Matrix ; Flow Cytometry ; Humans ; Inflammation ; Mice ; Microvessels ; Peptides* ; Thrombospondin 1 ; Vertebrates ; Wound Healing

No abstract available.
Animals ; Metaphase* ; Mice* ; Oocytes*

Angiogenesis is a fundamental biological process including endothelial cell adhesion, migration, invasion and tube formation. Integrin receptors of endothelial cells play important roles in angiogenesis. They mediate cell-cell contact and cell adhesion to extracellular matrix. Roles of integrins have been described for a number of cell types. ECV304 endothelial cells were known to overexpress alpha3beta1 integrin and to form tube like structure in 3-D Matrigel culture. However the function of alpha3beta1 integrin in endothelial cells remains to be determined. Therefore, we have investigated morphological characteristics of ECV304 cells and roles of alpha3beta1 integrin in angiogenesis. To elucidate several characteristics, ECV304 endothelial cells were compared with HUVEC in the aspect of morphology, localization of integrins, angiogenesis pattern. In addition, role of alpha3beta1 integrin were analyzed in the aspect of endothelial cell binding, migration, invasion and tube formation on Matrigel. The result showed that alpha3beta1 integrin overexpressed ECV304 endothelial cells showed strong adhesiveness to extracellular matrix proteins, and high migration and invasion activities. Furthermore, expression of alpha3beta1 integrin was increased according to time course during in vitro culture and was continuously strong in ECV304 cells on 3-D Matrigel culture. These results indicate that alpha3beta1 integrin is able to be a critical component in control of angiogenesis by regulation of cell adhesion, migration, invasion and tube formation of ECV304 endothelial cells.
Adhesiveness ; Biological Processes ; Cell Adhesion ; Endothelial Cells* ; Extracellular Matrix ; Extracellular Matrix Proteins ; Integrin alpha3beta1* ; Integrins

Angiogenesis is a series of processes that include endothelial proliferation, migration and tube formation. Vascular endothelial growth factor (VEGF) is regarded as a potent mediator of angiogenesis, vascular permeability and tumor cell growth in renal cell carcinoma. This study was designed to evaluate the expression of VEGF and the microvessel count (MVC) and to determine their prediction efficacies for prognosis in renal cell carcinoma. The relationship between the expression of VEGF and MVC were evaluated immunohistochemically in 50 patients with renal cell carcinoma who received a radical nephrectomy at Wonju Christian Hospital between 1989 and 1997. Microvessels were identified by immunostaining endothelial cells for CD-31 antigen. The mean follow-up was 96 months (3 - 133 months). Overall 5-year survival rate was 71.5%. VEGF was expressed in the tumor cell cytoplasm. Of the 50 tumors, 23 (46%) were weak to strongly positive for VEGF but 27 (54%) were unreactive. The respective 5-year survival rates for patients with positive and negative expressions of VEGF were 70% and 73% (p > 0.05). The overall mean MVC was 13.4 in a 400x field. Mean MVCs were significantly higher in VEGF-positive tumors (17.6 +/- 12.1) than in VEGF-negative tumors (9.9 +/- 5.4), and the MVCs of the high vascular density group and the low ascular density groups were significantly different. The 5-year survival rates of patients with high vascular density and low vascular density were 59% and 86%. The median survival period for patients with MVCs higher than or equal to 10 vessels/field was 85 months, whereas for those with MVCs lower than 10 vessels/field the median survival time was 102 months. These results suggest that MVC may be a better prognostic factor in renal cell carcinoma than the expression of VEGF.
Adult ; Aged ; Carcinoma, Renal Cell/*blood supply/*metabolism ; Endothelial Growth Factors/*metabolism ; Female ; Human ; Kidney Neoplasms/*blood supply/*metabolism ; Lymphokines/*metabolism ; Male ; Middle Age ; Neovascularization, Pathologic/*pathology ; Prognosis

BACKGROUND: Biochemical bone markers have been suggested to reflect postmenopausal high bone turnover. These markers could be useful in following response to hormone replacement therapy (HRT). But we have few studies about the sequential changes of biochemical bone markers and bone mass after HRT in Korean women, and it is unclear whether women with early menopause have different response to HRT from women with normal menopause. The aims of the present study were to see the sequential changes of biochemical bone markers and bone mass after HRT in Korean women, to examine whether a single baseline biochemical bone marker or a change in biochemical bone marker could predict subsequent bone mass, and to determine the difference of response to HRT between women with early menopause and women with normal menopause. METHODS: Postmenopausal women (n=21) were divided with into three groups according to their age at menopause (AAM): the first group with AAM < or = 43 years (early menopause group, n=7), the second group with 43 years < or = AAM < or = 50 years (n=4), and the third group with AAM > or = 50 years (normal menopause group, n=10). For the HRT, conjugated estrogen (0.625mg per day) and continuous or cyclic medroxyprogesterone (2.5-10mg per day) were administered. Bone mineral density (BMD) was measured at baseline and 12 months and biochemical bone markers were measured at baseline and 3, 6, and 12 months during HRT. RESULTS: Deoxypyridinoline, type 1 collagen N-telopeptide, bone alkaline phosphatase, and osteocalcin were significantly decreased at 3 months, and mean percent changes from baseline of bone resorption markers were larger than those of bone formation markers. At 12 months, BMD was significantly increased at lumbar spine and Ward's triangle. But BMD was not significantly increased at femur neck and femur trochanter. Two baseline bone markers (bone alkaline phosphatase and type 1 collagen N-telopeptide) correlated with changes of BMD but any changes of bone markers at 3, 6 months didn't correlate with changes of BMD. In early menopause group, changes of bone markers and BMD were larger than those in normal menopause group, but the difference between the two groups was not significant. CONCLUSION: All four bone markers showed significant reduction at 3 months, but bone resorption markers were decreased more markedly and rapidly, and some baseline bone markers can predict the change of BMD after HRT. The difference of response to HRT between early menopause group and normal menopause group was not significant.
Alkaline Phosphatase ; Bone Density* ; Bone Resorption ; Collagen Type I ; Estrogens ; Female ; Femur ; Femur Neck ; Hormone Replacement Therapy* ; Humans ; Medroxyprogesterone ; Menopause ; Osteocalcin ; Osteogenesis ; Spine

Numerous studies have shown that adenosine or adenosine agonists can stimulate angiogenesis. However, the effect of caffeine (a known adenosine receptor antagonist) on angiogenesis has not been previously studied. Accordingly, this study was undertaken to examine the effect of caffeine on angiogenesis and to clarify the mechanism involved. Chick chorioallantoic membrane assays were used to investigate the effect of caffeine on angiogenesis and proliferation assays using human umbilical vein endothelial cells (HUVECs), were used to study its effects on specific aspects of angiogenesis. The expressions of caspase-3 and Bcl-2 were examined by western blotting, immunofluorescence staining was used to identify HUVEC morphological changes, and fluorescence activated cell sorting (FACS) and DAPI staining were used to detect HUVEC apoptosis. Caffeine was found to inhibit blood vessel formation dose-dependently and to inhibit the proliferation of HUVECs time- and dose-dependently. FACS analysis and DAPI staining showed that inhibitory effect of caffeine on HUVEC proliferation was the result of apoptosis and the up-regulation of thrombospondin-1 (TSP-1). Furthermore, TSP-1 levels were down-regulated by NECA but were unaffected by CGS21680, indicating that caffeine regulated TSP-1 expression via adenosine A2B receptor. In addition, caffeine up-regulated caspase-3 and down-regulated Bcl-2 at the protein level. These results suggest that the inhibitory effect of caffeine on angiogenesis is associated, at least in part, with its induction of endothelial cell apoptosis, probably mediated by a caspase-3 dependent mechanism.
Adenosine ; Adenosine-5'-(N-ethylcarboxamide) ; Apoptosis ; Blood Vessels ; Blotting, Western ; Caffeine ; Caspase 3 ; Chorioallantoic Membrane ; Endothelial Cells ; Flow Cytometry ; Fluorescent Antibody Technique ; Glycosaminoglycans ; Human Umbilical Vein Endothelial Cells ; Indoles ; Phenethylamines ; Receptor, Adenosine A2B ; Receptors, Purinergic P1 ; Thrombospondin 1 ; Up-Regulation

This study was done to identify the normal and variants of saphenous tributaries in Korean adults. The pattern of confluence of saphenous tributaries, medial accessory saphenous, lateral accessory saphenous, superficial epigastric, superficial circumflex iliac and superficial external pudendal veins, was carefully examined in 249 lower limbs (right, 129; left, 120) of embalmed Korean cadavers (73 males and 56 females). The medial accessory saphenous vein drained into the great saphenous vein directly (in 82.3%) or by a common trunk (in 17.7%) with the superficial epigastric or superficial external pudendal vein. The lateral accessory saphenous vein entered the great saphenous (in 67.1%) or the femoral vein (in 32.9%) directly or, forming a common trunk with other saphenous tributaries. The superficial epigastric vein joined the great saphenous (in 77.1%) or the femoral vein (in 22.9%) directly or, by a common trunk with other saphenous tributaries. The superficial circumflex iliac vein reached the great saphenous (in 83.1%) or the femoral vein (in 16.9%) directly or, by a common trunk with other saphenous tributaries. The superficial external pudendal vein opened into the great saphenous (in 95.2%) or the femoral vein (in 4.8%) directly or by a common trunk with other saphenous tributaries. In Koreans, the incidence of the normal pattern of saphenous tributaries was 23.7% and in 76.3% any one of variant saphenous tributaries entered the femoral or the great saphenous vein by a common trunk with other saphenous tributaries.
Adult ; Cadaver ; Femoral Vein/*anatomy & histology ; Humans ; Iliac Vein/*anatomy & histology ; Korea ; Saphenous Vein/*anatomy & histology ; Thigh/*blood supply