• Journal of Life Science
• /
• v.26 no.12
• /
• pp.1367-1375
• /
• 2016

Cilostazol is known to be a selective inhibitor of phosphodiesterase III and is generally used to treat stroke. Our previous findings showed that cilostazol enhanced capillary density through angiogenesis after focal cerebral ischemia. Angiogenesis is an important physiological process for promoting revascularization to overcome tissue ischemia. It is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation. Here, we examined the modulatory effect of cilostazol at each step of the angiogenic mechanism by using human brain microvascular endothelial cells (HBMECs). We found that cilostazol increased the migration of HBMECs in a dose-dependent manner. However, it did not enhance HBMEC proliferation and capillary-like tube formation. We used a cDNA microarray to analyze the mechanisms of cilostazol in cell migration. We picked five candidate genes that were potentially related to cell migration, and we confirmed the gene expression levels by real-time PCR. The genes phosphoserine aminotransferase 1 (PSAT1) and CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$) were up-regulated. The genes tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), and RARRES3 were down-regulated. Our observations suggest that cilostazol can promote angiogenesis by promoting endothelial migration. Understanding the cilostazol-modulated regulatory mechanisms in brain endothelial cells may help stimulate blood vessel formation for the treatment of ischemic diseases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3379-3383
• /
• 2012

Objective: To investigate uPA and VEGF expression in esophageal cancer and relations with tumorous invasion and metastasis. Methods: Immunohistochemistry was used to detect uPA and VEGF expression in the normal epithelial tissue of esophageal mucosa and cancer tissue and detect CD34 labeled micrangium and analyze the relationships with clinical pathological features and tumor angiogenesis. Results: Positive rates for uPA and VEGF protein expression were significantly greater in esophageal cancer than normal epithelial tissue (P < 0.05), the two being linked (P <0.05). In addition, uPA and VEGF protein expression of the high microvessel density (MVD) group was significantly lower than in the low MVD group (P < 0.05), with relation to clinical pathological staging, differentiation and lymph node metastasis (P < 0.05). Conclusion: In esophageal cancer tissue, uPA and VEGF proteins are overexpressed and promote tumor angiogenesis, indicative of a poor prognosis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4453-4458
• /
• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• Archives of Plastic Surgery
• /
• v.37 no.5
• /
• pp.526-530
• /
• 2010

Purpose: With the recent recognition of the importance of soft-tissue fillers, fat grafting has been assumed an increasingly important role as both an adjunctive and a primary procedure in aesthetic and reconstructive surgery. The main problem in achieving long-term soft-tissue augmentation is partial absorption of the injected fat and hence the need for overcorrection and re-injection. The purpose of this study is to improve the viability of the injected fat by the use of Lipo-PGE1. Methods: Human adipose tissue, obtained by suctionassisted lipectomy, was re -injected into the subcutaneous layer in the scalp of ICR mice. Lipo-PGE1 ($0.5{\mu}g$/kg) was injected intravenously in experimental group for 7 days from the operation day and saline was injected in control group. There were 5 animals in each group. The animals were euthanized 4 weeks after the procedure. Graft weight and volume were measured and histologic evaluation was performed. Result: Histologic analysis demonstrated significantly less cyst formation and less inflammatory reaction in the group treated with Lipo-PGE1. No significant difference was found between the groups regarding graft volume or the other histologic parameters investigated. Significant differences were demonstrated in microvascular density count. Conclusion: Less cyst formation, less inflammation, more angiogenesis indicating improved quality of the injected fat can be obtained by the addition of Lipo-PGE1. Further studies of various dosages of Lipo-PGE1 and their long-term effect are required before these encouraging results could be applied clinically.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
• /
• 2015.05a
• /
• pp.622-624
• /
• 2015

Tumor hypoxia caused by the unique characteristics of solid tumor sites such as lowered vascular density, irregular vasculature, longitudinal oxygen gradient, and unbalanced oxygen consumption has decreased therapeutic efficacy in several clinical trials such as radiation, chemotherapy, and surgery. Hence, tumor oxygenation studies at microvascular levels are important to provide better understanding of the complexity of microvasculature oxygen transport and exchange with tissue. However, polarographic microelectodes, was employed to measure $pO_2$ at the microvasculature level, but it is difficult to perform and does not provide significant spatial and temporal information of oxygen delivery. In this research, we introduce the hyperspectral imaging system able to provide a wide range of vascular characteristics by spatial maps on hemoglobin saturation information for better understanding of the relationship between blood oxygen delivery, hypervascularity, aberrant angiogenesis at microvasculature levels during tumor growth.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
• /
• v.23 no.1
• /
• pp.71-85
• /
• 1993

The purpose of the study was to investigate the effects of the single and fractionated irradiation on the microvascular structure of the submandibular gland in rats. For this study, 90 Sprague-Dawley strain rats were irradiated to their neck region with equal split doses of 9Gy for a 4 hours interval and 15Gy single dose by 6MV X-irradiation and sacrificed on the 1st, 3rd, 7th, 14th and 27th day after irradiation. The author observed histological changes at Hematoxylin and Eosin staining and PAS staining under a light microscope, and also observed distribution and structural changes of the microvasculature in rat submandibular gland using a scanning electron microscope by forming vascular resin casting. The results were as follows: 1. In the light microscopic examination, the microvasculature was slightly dilated and decreased in number on the 1st day after irradiation, and increase in number of microvasculature was observed on the 3rd day after irradiation. And then distribution of microvasculature was markedly increased on the 7th day after iradiation, but decreased on th 14th day after irradiation again. Such changes were greater in the single irradiated group than in the fractionated irradiated group. 2. The reaction to PAS staining on glandular cell was decreased on the 1st and the 3rd day after irradiation, and recovered on the 7th day after irradiation. The reaction was decreased on the 14th day after irradiation again, and recovered on the 28th day after irradiation. Changes were more apparent in the single irradiated group. 3. In the scanning electron microscopic examination, early changes of microvasculature were decreased capillary density, dilation of conduits and meandering. Increased capillary dentsity or anastomosis due to vascular reproduction and smooth curved running were observed on the 7th and 14th day after irradiation. Decreased capillary and smooth running tendency were observed on the 28th day after irradiation again. Such changes were greater in the single irradiated group than in the fractionated irradiated group.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
• /
• v.22 no.1
• /
• pp.43-53
• /
• 1992

The purpose of this study was to investigate the effects of irradiation on the microvascular structure of the submandibular gland in rats. For this study, 110 male rats were singly irradiated with the dose of 10Gy or 20Gy to their neck region by 6MV X-irradiation and sacrificed on the 1st, 3rd, 7th, 14th and 28th day after irradiation. The author observed distribution and structural changes of the microvasculature in rat submandibular glands using a scanning electron microscope by forming vascular resin casting. The author observed ultrastructural changes of the endothelial cells using a transmission electron microscope, and also histologic changes using a light microscope at Hematoxylin and Eosin staining and PAS staining process. The results of the irradiation effects on the microvasculature in rat submandibular gland were as follows: By light microscopic examination, the dilation of small vessels were observed until the 7th day after irradiation. After then, the vascular constriction and decrease in number of small vessels were noticed. Changes were greater on 20Gy irradiated group than on lOGy irradiated group. The reaction to PAS staining at acinar cells was decreased just after irradiation, but gradually recovered with days. There was no specific difference between two irradiated groups. By scanning electron microscopic examination, general findings on the two irradiated groups were similar. The dilation of conduits and meandering were observed on the 3rd day after irradiation. Decrease of capillary density and blunt ended small vessels were appeared on the 7th day after irradiation. After that, findings of the tortuous and twisted vascular running and coarseness of capillary lumen were increased. Changes were greater on 20Gy irradiated group than on l0Gy irradiated group. By transmission electron microscopic examination, increase of the formation of cytoplasmic process was observed on the 3rd day after irradiation. After that, swelling of endothelial cell and bridge formation of cytoplasmic processes were also observed, but destruction of endothelial cell and loss of basement membrane were observed only on 20Gy irradiated group on the 28th day after irradiation.

• Journal of Gastric Cancer
• /
• v.2 no.4
• /
• pp.195-199
• /
• 2002

Purpose: Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) is the most significant angiogenic factor and a selective mitogen for endothelial cells. VEGF, also known as the vascular permeability factor, acts on endothelial cells to increase microvascular permeability and directly stimulate the growth of new blood vessels. Several studies have reported that the expression of VEGF is correlated with hematogenous recurrence via angiogenesis in gastric carcinomas. This research evaluated the relationship between the expression of VEGF and hepatic and peritoneal recurrence in gastric carcinomas. Materials and Methods: Thirty specimens resected from patients with primary gastric carcinomas who had undergone curative resections were divided into three group: Group I, early gastric carcinomas without recurrence; Group II, advanced gastric carcinomas with hepatic recurrence; and Group III, advanced gastric carcinomas with peritoneal recurrence. The expression of VEGF and the density of the microvessel count were examined using immunohistochemistry. Results: 1) The expression of VEGF in Group II and Group III ($63.2\pm\24.3\%$) was stronger than that in Group I ($7\pm\4.2\%$). The expression of VEGF in Group II ($76.5\pm\13.2\%$) was stronger than that of the Group III ($50\pm\14.2\%$) (P<0.05). 2) The microvessel count in Group II ($49.9\pm14.5$) was more than that in Group I ($8.6\pm2.6$) and Group III ($29.1\pm18.1$) (P<0.05). 3) The microvessel count was increased significantly with increasing the expression of VEGF. Conclusions: The expression of VEGF is associated with advanced stomach cancer and hepatic recurrence has a higher expression of VEGF than peritoneal recurrence with neovascularization. Thus the expression of VEGF can be considered to be a useful indicator of recurrence in gastric carcinoma and especially in hepatic recurrence.

• Archives of Plastic Surgery
• /
• v.34 no.3
• /
• pp.291-297
• /
• 2007

Purpose: Platelet-rich plasma(PRP) contains protein growth factors, which are actively secreted by platelets to promote wound healing. However, it is not clear whether the injection of PRP into the autologous fat grafts increases the survival rate and the degree of angiogenesis. Methods: New Zealand White rabbit ears were injected fat with PRP, saline, insulin or isoproterenol (n=8/each group) for observation of the survival and degree of angiogenesis of the injected fat. The volume of the harvested fat and the degree of angiogenesis from dorsum of rabbit ears were evaluated 4, 8, and 12 weeks after the autologous fat graft. The degree of angiogenesis was measured with microvascular density (MVD) counts. Results: The volume of harvested fat decreased in a time-dependent manner after autologous fat grafts, but the decrease rate in volume of harvested fat was slower in PRP-injected group compared to that of other control groups. The difference in the volume of the harvested fat between PRP-injected group and other control groups became significant from 4 weeks after the autologous fat graft, and was maintained up to 12 weeks. However, there was no significant difference between PRP-injected group and insulin-injected group 8 and 12 weeks after the autologous fat graft. On the contrary, MVD counts increased in a time-dependent manner after autologous fat grafts. The MVD counts were significantly higher in PRP-and insulin-injected groups than in other control groups from 4 weeks after the autologous fat graft, and these differences were maintained up to 12 weeks. There was no correlation between mean platelet numbers and the volume of harvested fat. Conclusion: The present study demonstrates that PRP-injection into autologous fat grafts increases the survival rate and the degree of angiogenesis. Thus, PRP injection with autologous fat grafts would be a promising tool for maintaining the volume of the grafted fat.

• Journal of Nutrition and Health
• /
• v.55 no.3
• /
• pp.348-358
• /
• 2022

Purpose: Hyperglycemia accelerates the formation of advanced glycation end products (AGEs), a group of compounds formed via non-enzymatic glycation/glycoxidation. Type 2 diabetes mellitus (T2DM) is related to oxidative stress, resulting in some overgeneration of AGEs. The accumulation of AGEs in T2DM patients leads to increased inflammation, DNA damage, tissue damage, progression of diabetic microvascular disease, and nephropathy. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme. Expression of HO-1 in the endothelium and in muscle monocytes/macrophages was upregulated upon exposure to reactive oxygen species or oxidized low-density lipoprotein. Cells activated by oxidative stress are reported to release HO-1 in the serum. In the current study, we discuss the oxidative status according to the level of AGEs and the association of HO-1 with AGEs or urinary DNA damage marker in type 2 diabetic Korean patients. Methods: This study enrolled 36 diabetic patients. Subjects were classified into two groups by serum AGEs level (Low AGEs group: < 0.85 ng/mL serum AGEs; High AGEs group: ≥ 0.85 ng/mL serum AGEs). Body composition was measured using bioelectrical impedance analysis. Blood and urinary parameters were measured using commercial kits. Results: No significant differences were observed in the general characteristics and body composition between the two groups. Serum HO-1 concentration was significantly higher in the High AGEs group than in the Low AGEs group. After adjustment of age and gender, a correlation was performed to assess the association between serum HO-1 and serum AGEs or urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Our results indicate that serum HO-1 is positively correlated with serum AGEs and urinary 8-OHdG. Conclusion: Taken together, our results indicate that in diabetes patients, a high level of HO-1 is associated with a high concentration of AGEs and 8-OHdG, probably reflecting a protective response against oxidative stress.