• 생명과학회지
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• 제26권12호
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• pp.1367-1375
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• 2016

Cilostazol은 phosphodiesterase III의 선택적 저해제로 알려져 있으며, 뇌졸중 치료에 일반적으로 사용되고 있다. Cilostazol을 처리한 경우, 국소 뇌허혈이 발생한 후에 혈관신생을 통해서 혈관형성이 향상된다는 것을 본 연구자들이 발표하였다. 혈관신생은 조직의 허혈상태를 극복하기 위해서 혈관재생을 촉진하는 중요한 과정으로써, 혈관내피세포의 증식, 이동, 모세관구조 형성의 다단계 과정으로 구성되어 있다. 이에 본 연구에서는 인간 뇌혈관내피세포를 이용하여 cilostazol이 혈관신생의 각 단계들에 어떤 영향을 미치는지 조사하였다. Cilostazol은 농도의존적으로 뇌혈관내피세포의 이동성을 촉진하였으나, 뇌혈관내피세포의 증식과 모세관구조 형성에는 영향을 미치지 않았다. Cilostazol이 세포이동을 조절하는 기전을 분석하기 위해서 cDNA microarray를 수행하였고, 세포이동에 관련성이 있는 5종의 후보 유전자들을 선택하여 real-time PCR을 통해 해당 유전자의 발현을 검증하였다. Cilostazol에 의해서 발현양이 조절되는 유전자들로써, phosphoserine aminotransferase 1 (PSAT1)와 CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$)은 발현이 증가하였고, tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), RARRES3는 발현이 감소하였다. 이상의 결과를 통해서 cilostazol이 혈관내피세포의 이동을 촉진하여 혈관신생을 향상시킬 수 있음을 제안할 수 있으며, 뇌혈관내피세포에 대한 cilostazol의 조절기전에 대해서 더욱 상세히 규명을 한다면 혈관형성을 통하여 허혈성 질환을 치료할 수 있는 유용한 정보가 될 것으로 기대한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3379-3383
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• 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
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• 제13권9호
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• pp.4453-4458
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• 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
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• 제37권5호
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• pp.526-530
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• 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.

• 한국정보통신학회:학술대회논문집
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• 한국정보통신학회 2015년도 춘계학술대회
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• pp.622-624
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• 2015

암 세포 주변의 저산소증은 방사선, 항암치료제, 절제술 등을 이용한 항암치료법에 중요한 역할을 하는데, 특히 암세포 주변의 모세혈관 내에서의 산소의 이동 분석은 암의 발달 및 전이, 주변 혈관의 생성과 변이에 직간접적 영향을 미친다. 따라서 현재 암 병변 주변의 모세혈관 내 헤모글로빈 산소포화도를 측정하고 혈관의 생성 및 변이상태를 측정하는 연구가 활발하게 진행되고 있지만, 대부분의 계측장비는 침습적인 방법으로 진행되며, 해상도 또한 기대이하의 공간 및 시간영역을 제공하는 한계가 있다. 따라서 본 연구에서는 비침습적 헤모글로빈 산소포화도 이미지와 다양한 이미지프로세싱 기법을 이용하여 실시간 혈관변화의 분석을 통해 암 혈관 생성 및 변이의 특성을 제공할 수 있는 초분광 이미징 시스템 활용 방법을 제시하고자 한다.

• 치과방사선
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• 제23권1호
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• pp.71-85
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• 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.

• 치과방사선
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• 제22권1호
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• pp.43-53
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• 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
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• 제2권4호
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• pp.195-199
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• 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
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• 제34권3호
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• pp.291-297
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• 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
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• 제55권3호
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• pp.348-358
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• 2022

본 연구는 한국에서 최초로 시행되는 연구로서, 성인 제2형 당뇨환자에서 혈청 AGEs의 농도에 따라 두 군으로 나눈 뒤 신체계측 및 체조성, 영양소 섭취량, 생화학적 지표를 비교 분석한 연구이다. Low AGEs group과 High AGEs group의 평균 AGEs는 각각 0.4 ± 0.2, 3.4 ± 1.7 ng/mL로 나타났다. 항산화 효소인 HO-1은 High AGEs group이 Low AGEs group에 비해 유의적으로 높게 나타났다. 또한, 전체 연구참여자를 대상으로 연령과 성별을 보정한 후 상관관계를 분석한 결과, 혈청 HO-1 농도와 혈청 AGEs 농도 및 소변 8-OHdG 농도는 양의 상관관계를 가지는 것으로 나타났다. 본 연구를 통해 혈청 HO-1은 당뇨환자 특이적 지표인 AGEs와 더불어 DNA 손상 지표에도 예민하게 반응하는 것을 확인하였으며, 추후 한국 당뇨환자의 산화적 스트레스와 합병증 연구의 근거자료로 널리 사용될 수 있을 것으로 사료된다.