• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.10-18
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• 2006

Epithelial to mesenchymal transition (EMT) is an important etiologic factor for the development of peritoneal fibrosis in CAPD patients. Mesothelial cells are main source of trans-differentiated fibroblasts under stress from the bioincompatible peritoneal dialysate. In our study there was no difference in dialysate TGF-${\beta}$ and VEGF between the low and high GDP groups during an initial 12 months. However, after adjusting with D-CA125, the low GDPs group showed a significantly lower D-TGF-${\beta}$/D-CA125 and D-VEGF/CA125 during the initial 12 months. Among the adjusted peritoneal growth factors for CA125, VEGF/CA125 and TGF-b/CA125 were factors significantly associated with greater EMT in this study. Adjustment of the peritoneal growth factor for effluent CA125 (surrogate for mass of HPMCs) revealed significant association with EMT suggesting that the fibroblastoid transition from HPMCs could be affected by the amount of intraperitoneal growth factors (TGF-b, VEGF) per unit mass of HPMCs. There was significant improvement in both cell score and D-CA125 at the sixth and 12th months after switching from a high GDPs solution to a low GDPs solution. Use of icodextrin solution in patients who had average peritoneal transport showed not only better systemic effects such as decreased glucose absorption via dialysate but also preservation of the peritoneum, including less EMT and high mesothelial bulk mass. In conclusion, Therapy with low GDP solution including icodextrin may positively impact preservation of the peritoneal membrane integrity and prevention of peritoneal fibrosis with time on PD.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.2053-2058
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• 2013

Background: Formation of new blood vessels is necessary for the development and spread of neoplasms more than 1 mm3 in volume, angiogenesis being responsible for formation of new from pre-existing blood vessels. Vascular endothelial growth factor (VEGF) is pivotal and the best studied angiogenic factor in all human cancers. Therefore we designed this study to investigate the role of VEGF-A and VEGF-C in prostate cancer in comparison with BPH controls in a north Indian population. Methods: In this case-control study a total of 100 subjects were included on the basis of confirmed histopathological reports, out of which 50 were prostate cancer patients and the other 50 were BPH patients with PSA levels >2 ng/ml and abnormal digital rectal examination (DRE) findings during September 2009 to August 2011 from the Department of Urology, KGMU, Lucknow, India. Plasma levels of VEGF were determined using quantitative immunoassay (ELISA-enzyme linked immunosorbent assay). Statistical analysis was carried out using SPSS 15.0 version. Results: The mean age of prostate cancer ($67.6{\pm}5.72$) patients was significantly higher (p=0.005) than BPH ($63.6{\pm}7.92$) patients. Expression of VEGF-A was not significantly higher in disease stage C1 than D1 or D2 and A or B (p=0.13) while the level of VEGF-A was significantly higher (p=0.04) in prostate cancer as compared to BPH subjects (PCa=13.0 pg/ml, BPH=6.8 pg/ml). Levels of VEGF-C were similar in both groups (PCa=832.6 pg/ml, BPH=823.7 pg/ml). In ROC curve, the area under curve (AUC) was 0.70 (95%CI: 0.60-0.80) and the cut-off value for which a higher proportion of patients was correctly classified (20%) was 26.0 pg/mL. Conclusion: Although VEGF-A is increased in cancer prostate patients a statistically significant correlation could not be established in this study. VEGF-C was not found to be a useful biomarker.

• 대한화장품학회지
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• 제42권4호
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• pp.329-336
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• 2016

진피 상층부 모세혈관은 젊은 사람에 비해 노인에서 그 수와 크기가 감소되어 있어 피부에서 모세혈관이 차지하는 비율이 나이에 따라 급격히 낮아진다. 연교는 물푸레나무과에 속하는 개나리 열매를 건조한 것으로 주로 염증성 또는 항균성 질환에 오랫동안 사용되어져온 약재로서 지금까지 피부 혈관신생과 관련된 효능은 보고되지 않았다. 따라서 본 연구에서는 연교 추출물이 혈관신생과 관련된 인자들에 미치는 영향을 피부 각질형성 세포주를 이용하여 조사하고자 하였다. 우리는 먼저 연교 추출물이 혈관신생과 관련된 인자들의 발현에 어떤 영향을 주는지 알아보고자 각질형성세포에 연교 추출물을 처리하고 혈관신생과 관련된 55개 단백질의 발현을 분석하였다. 발현 변화를 보인 인자들 중 혈관내피세포 성장인자(VEGF, vascular endothelial growth factor)는 강력한 혈관신생 촉진인자로서 연교 추출물에 의해 유의하게 발현이 증가되었다. 따라서 연교 추출물이 VEGF 생성에 미치는 영향에 대해 자세히 알아보고자 연교 추출물을 농도별로 세포에 처리하고 단백질 발현과 mRNA 발현 변화를 조사한 결과, 연교 추출물은 VEGF의 유전자 수준뿐만 아니라 단백질 수준의 발현을 2배이상 농도 의존적으로 증가시켰다. 다음으로 연교 추출물에 의한 VEGF 발현 증가에 관여하는 신호전달 기전을 밝히고자 MAPK 활성을 살펴본 결과, 연교 추출물을 세포에 처리하면 5 min 내 p38 MAPK의 활성이 관찰되었으며, 특이적 억제제 전처리를 통해 p38 MAPK 활성을 억제하면 연교 추출물을 처리하더라도 VEGF의 유전자 및 단백질 발현이 완전히 억제됨을 확인하였다. 이러한 결과로부터 연교는 피부 각질형성세포에 작용하여 p38 MAPK 활성을 통해 VEGF 생성을 유도함을 알 수 있었고, 피부에서 노화에 따른 표피아래 모세혈관 손상을 개선하는데 도움을 줄 수 있는 후보 물질로서 연교의 새로운 효능을 제안한다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제31권5호
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• pp.363-369
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• 2005

Purpose: To determine the role of Insulin-like Growth Factor-I (IGF-I) in the regulation of Vascular Endothelial Growth Factor (VEGF) expression in MG-63 cells and then to find the mechanism b which this regulation occurs. Materials and methods: MG-63 cells were grown to confluence in 60-mm dishes. To determine the effects of IGF-I on expression of VEGF mRNA according to time and concentration, the cells were treated with 10 nM IGF-I, following isolation of total RNA and Northern blot analysis after 1, 2, 4, 8, 12, 24 hours and after 2 hours of treatment with 0.5, 2, 10, 25, 50 nM IGF-I respectively, isolation of total RNA and Northern blot analysis were followed. To determine the mechanism of action of IGF-I, inhibitors such as hydroxyurea $(76.1\;{\mu}g/ml)$, actinomycin D $(2.5\;{\mu}g/ml)$, cycloheximide $(10\;{\mu}g/ml)$ were added 1 hour after treatment of 10 nM IGF-I. Results: 1. the expression of VEGF mRNA was increased with treatment of IGF-I. 2. The expression of VEGF mRNA was increased according to time-and concentration dependent manner of IGF-I. 3. The effect of IGF-I was decreased by hydroxyuera, actinomycin D, but not by cycloheximide. Conclusion: IGF-I regulate the expression of VEGF mRNA in the level of DNA synthesis and transcription. These results could suggest that IGF-I plays an important role in angiogenesis in the process of new bone formation and remodeling.

• Clinical and Experimental Reproductive Medicine
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• 제34권1호
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• pp.33-39
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• 2007

목 적: 자궁강 내 인공수정을 위한 과배란유도 시 혈청 vascular endothelial growth factor (VEGF) 농도가 과배란유도의 결과를 반영할 수 있는지를 확인해 보고자 하였다. 연구방법: 과배란유도 후 자궁강 내 인공수정을 시행 받은 49 명의 불임여성을 대상으로 hCG 투여 일에 혈청을 얻어 VEGF-A 및 estradiol 농도를 측정하였다. 과배란유도는 clomiphene citrate (100 mg/d on day 3$\sim$7) 와 human menopausal gonadotropin (150 IU every other day starting on day 5) 병합요법을 이용하였다. hCG 투여 일에 17mm 이상의 성숙난포 수와 자궁내막 두께를 동시에 측정하였다. 결 과: 혈청 VEGF-A 농도는 성숙난포 수, estradiol 농도 및 자궁내막 두께와는 무관하였던 반면 성숙난포 수와 estradiol 농도는 양의 비례관계를 보였다. 혈청 VEGF-A 농도는 성숙난포 수가 2 개 이하인 저 반응 군과 6 개 이상인 고 반응 군에서 통계적으로 유의하지는 않지만 낮은 수치를 보였다. 결 론: 혈청 VEGF-A 농도는 자궁강 내 인공수정 시술 시 과배란유도의 결과와 무관한 것으로 사료되지만 저 반응 군과 고 반응 군에서 낮은 농도를 보이는 것으로 보아 이들을 대상으로 한 추가 연구가 필요할 것으로 판단된다.

• Clinical and Experimental Reproductive Medicine
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• 제31권4호
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• pp.235-244
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• 2004

Objective: The effects on spermatogenesis by expression of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were investigated. Materials and Methods: Testicular specimens were obtained from 40 infertile males due to primary testicular failure and from 10 fertile males with other urologic problems. The specimens of infertile males were devided into 4 groups according to histologic findings; Sertoli cell only syndrome (A), maturation arrest (B), hypospermatogenesis (C) and sloughing and disorganization (D). VEGF and ET-1 expression were detected with immunohistochemical stain. Results: VEGF expression on Leydig cell was detected in all cases. But, VEGF expression rates on germ cell were significantly higher in infertile group B, C, D compared to that of the control group (p<0.05). ET-1 expression rates on Leydig cell was significantly lower in all infertile group compared to that of the control group (p<0.05). But, ET-1 expression rates on Sertoli cell was significantly higher in all infertile group compared to that of the control group (p>0.05). In germ cell of infertile group, LH, FSH and prolactin were significantly decreased, and estradiol is increased in positive stain group on ET-1 immunohistochemical stain (p<0.05). VEGF and ET-1 expression were not correlated mean seminiferous tubule diameter (p>0.05). Conclusions: Abnormal spermatogenesis would be reflected in VEGF expression in germ cell.

• Childhood Kidney Diseases
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• 제14권2호
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• pp.166-173
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• 2010

목 적 : 복막투석환자에서 복막의 용질이동성에 영향을 미치는 요인으로 유전적 요인과 임상적 요인이 있다. 복막평형검사는 복막투석환자의 복막 용질이동속도를 평가하는 데에 유용한 검사로, 본 연구에서는 소아 복막투석 환자에서 복막평형검사 결과를 이용하여 혈관내피성장인자(VEGF)의 유전자 다형성과 복막 용질이동성의 상관관계를 연구하였다. 방 법 : 서울대학교 어린이병원과 삼성서울병원의 소아 복막투석환자 중에서 복막염의 병력이 없고 복막투석 시작한 지 1년 이내에 복막평형검사가 시행된 환자를 대상으로 하였다. VEGF 유전자 -2578 C/A, -14978T/C, -1154G/A, -634G/C, +936 C/T의 단일 유전자다형성분석을 시행하였고 VEGF 유전자 다형성의 분포와 복막평형검사 결과간의 상관관계를 분석하였다. 결 과 : 복막평형검사를 분석한 결과, 4시간 크레아티닌의 투석액/혈장비(D/P creatinine)는 $0.56{\pm}0.13$였고 4시간 투석액/0시간투석액포도당비(D/$D_0$ glucose)는 $0.43{\pm}0.11$였다. 배수체 CTGGC의 이형접합체 또는 동형접합체인 경우가 배수체 CTGGC를 가지지 않은 경우에 비해 높은 4시간 D/P creatinine ($0.67{\pm}0.12$ vs $0.50{\pm}0.09$, P=0.007)과 은 4시간 D/$D_0$ glucose ($0.35{\pm}0.12$ vs $0.47{\pm}0.08$, P=0.037)를 보였다. 결 론 : VEGF 유전자 다형성은 복막 용질이동성에 영향을 미칠 수 있다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제35권1호
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• pp.1-12
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• 2013

Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

• 한국수정란이식학회지
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• 제22권4호
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• pp.213-218
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• 2007

This study was performed to investigate the effect of VEGF on in vitro maturation of porcine oocytes. The base medium for IVM, TCM-199 was supplemented with 0.6 mM cysteine, 0.91 mM pyruvate, 10 ng/ml epidermal growth factor, $75{\mu}g/ml$ kenamycin, $1{\mu}g/ml$ insulin and 10% (V/V) porcine follicular fluid (pFF) as a Group A; Group B was consists of Group A plus 5 ng/ml VEGF; Group C was consists of replacement of pFF by 10% PVA and Group D: was consists of Group C plus 5 ng/ml VEGF. 1. The maturation rate was significantly higher (p<0.05) in control and VEGF+pFF group than other two groups ($76.1{\pm}9.6,\;78.9{\pm}6.0\;vs\;60.4{\pm}14.2\;and\;58.3{\pm}14.3$, respectively). 2. Addition of VEGF without pFF showed a negative effect on oocytes maturation and about 58.26% oocytes were reached to M-II stage. 3. In the parthenogenetic development, the cleavage rate was significantly higher (p<0.05) in control and VEGF+pFF group ($73.2{\pm}1.8\;and\;64.6{\pm}1.1$, respectively) than other groups ($47.9{\pm}1.8\;and\;48.3{\pm}1.7$, respectively). 4. The blastocyst formation rate was significantly higher (p<0.05) in VEGF+pFF group ($32.6{\pm}2.4$) compared to control and other groups. 5. There was no significant difference in cell numbers (inner cell mass or trophectoderm) among these groups.

• BMB Reports
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• 제53권10호
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• pp.533-538
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• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.