• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권1호
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• pp.41-51
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• 2008

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제41권1호
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• pp.11-18
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• 2015

Objectives: The goal of this study was to determine the correlation of clinicopathological factors and the up-regulation of vascular endothelial growth factor (VEGF) expression in oral squamous cell carcinoma. Materials and Methods: Immunohistochemical staining of VEGF and quantitative real-time polymerase chain reaction (RT-PCR) of VEGF mRNA were performed in 20 specimens from 20 patients with oral squamous cell carcinoma and another 20 specimens from 20 patients with carcinoma in situ as a controlled group. Results: The results were as follows: 1) In immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, high-level staining of VEGF was observed. Significant correlation was observed between immunohistochemical VEGF expression and histologic differentiation, tumor size of specimens (Pearson correlation analysis, significance r>0.6, P<0.05). 2) In VEGF quantitative RT-PCR analysis, progressive cancer showed more VEGF expression than carcinoma in situ. Paired-samples analysis determined the difference of VEGF mRNA expression level between cancer tissue and carcinoma in situ tissue, between T1 and T2-4 (Student's t-test, P<0.05). Conclusion: These findings suggest that up-regulation of VEGF may play a role in the angiogenesis and progression of oral squamous cell carcinoma.

• Clinical and Experimental Pediatrics
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• 제46권2호
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• pp.167-172
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• 2003

목 적 : 소아 심장병의 주종을 이루고 있는 선천성 심장병 환아들에서 폐동맥 고혈압은 비교적 흔히 발생하지만 매우 치료하기 어려운 합병증이다. 폐동맥 고혈압의 원인과 치료 및 예방에 대해서는 아직 많이 알려지지 않은 실정이므로 이의 원인을 산소결핍이라는 전형을 이용하여 VEGF란 유전인자의 차원에서 규명하고, 나아가서는 폐동맥 고혈압의 치료 및 예방책을 마련하기 위하여 이 연구를 시행하였다. 방 법 : 폐동맥 평활근 세포는 생후 6주 Fischer rat의 주폐동맥을 적출하여 작은 조각으로 잘라 20% fetal bovine serum을 첨가한 DMEM 배지를 사용하여 5% 이산화탄소 배양기에서 배양하였다. 배양된 세포는 평활근 세포에만 선택적으로 염색되는 평활근 myosin과 ${\alpha}$-actin 항체를 이용하여 염색함으로써 순수 평활근 세포임을 확인하였다. 5% 이산화탄소 배양기에서 배양한 대조군 세포와 1 또는 3% $O_2$ tension에서 배양한 실험군 세포에서의 VEGF 발현 차이와 starvation한 군과 하지 않은 군에서의 VEGF 발현 차이를 RT-PCR과 northern blotting을 이용하여 비교하였다. 결 과 : 대조군과 저산소 조건에서 배양한 실험군에서 VEGF 발현 정도는 차이가 없었다. 결 론 : 아직 국내에서는 유전인자 차원에서의 폐동맥고혈압의 원인규명이나 이에 따른 치료에 대한 연구가 전혀 없는 상태이며, 이 연구에 이어 신생쥐와 성숙쥐와의 차이점 및 나아가서 사람과 쥐의 폐동맥 평활근 세포의 차이점 등을 규명할 예정이며, 이번 연구 결과를 바탕으로 폐동맥 고혈압의 원인기전 규명, 치료 및 예방방법 개발에 기여하고자 한다.

• Journal of Korean Neurosurgical Society
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• 제29권10호
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• pp.1303-1308
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• 2000

Objectives : It has been known that vascular endothelial growth factor(VEGF), as an endothelial cell-specific mitogen, induces angiogenesis, and possesses vascular permeability and procoagulant properties. Peritumoral brain edema(PTBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma and proteins through the interendothelial spaces. The correlation between pathological grading, PTBE, neovascularization, and the expression of VEGF were analyzed in 31 patients with astrocytic tumors. Methods : Astrocytic tumor samples(8 astrocytomas, 14 anaplastic astrocytomas, and 9 glioblastomas) from 31 patients( 21 males and 10 females : average age $37{\pm}24$ years) who underwent surgery were examined retrospectively for the expression of VEGF and CD31(microvasculature) immunohistochemically. The extent of PTBE was examined by using preoperative CT or MRI as an edema index(EI). In addition to VEGF and CD31, several causative factors including tumor size, histologic type were compared with EI. Results : Only one of 8 astrocytomas, and majority of high grade(21 of 23 anaplastic astrocytomas and glioblastomas) tumors demonstrated PTBE(p<0.05). The majority of high grade tumors showed higher expression of VEGF (p<0.01). High grade tumors showed even higher CD31 expression(p<0.05), however, there was no close correlation between expression of VEGF and CD31. The EI was increased significantly, just as VEGF(p<0.01), but CD31 expression was not correlated with high EI. Conclusion : These data suggest that VEGF expression is closely correlated with PTBE and histological grading in astrocytic tumors. Microvasculature(CD31) in tumors is highly correlated with histological grading, however, shows no correlation with the expression of VEGF and PTBE.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권2호
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• pp.55-65
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• 2009

Purpose: We determined the therapeutic effects of blockade of epidermal growth factor(EGF) and vascular endothelial growth factor(VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma(OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor(orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. Results: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators(pMAPK and pAkt), decreased proliferative index, decreased microvessel density(MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.

• BMB Reports
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• 제40권3호
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• pp.439-443
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• 2007

Tumor growth and metastasis are dependent on angiogenesis, and endothelial cell invasion and migration are apparent means of regulating tumor progression. We report here that saxatilin, a snake venom-derived disintegrin, suppresses the angiogenesis-inducing properties of NCI-H460 human lung cancer cells. Culture supernatants of NCI-H460 cells are able to induce human umbilical vascular endothelial cell (HUVEC) invasion and tube formation. However, treatment of the cancer cells with saxatilin resulted in reduced angiogenic activity of the culture supernatant. This suppressed angiogenic property was found to be associated with the level of vascular endothelial growth factor (VEGF) in the culture supernatant. Further experimental evidence indicated that saxatilin inhibits VEGF production in NCI-H460 cells by affecting hypoxia induced factor-1$\alpha$ (HIF-1$\alpha$) expression via the Akt pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1881-1895
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• 2015

Background: The vascular endothelial growth factor family has been implicated in tumorigenesis and metastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/VEGFR co-expression, in patients with non-small lung cancer remains controversial. Materials and Methods: Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled by using a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed. Results: 74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated separately with poor survival. Especially, VEGFA over-expression was an independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker. Conclusions: The expression of VEGFA (particularly in SCC and early stage NSCLC), VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable as prognostic biologic markers.

• 생명과학회지
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• 제24권4호
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• pp.337-342
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• 2014

Resveratrol (RSV)은 천연 폴리페놀계 화합물로 세포분열, 성장, 세포이동 등과 같은 다양한 효과가 보고되었다. Angiogenin (ANG)은 Vascular endothelial growth factor (VEGF)와 함께 세포의 증식, 신생혈관형성, tubular structures의 형성, 세포이동 등을 이끄는 중요한 단백질이다. 본 연구에서는 RSV에 의한 세포이동효과를 HeLa 세포에서 관찰하였다. Real-time PCR을 통해 HeLa 세포에 RSV $0{\sim}50{\mu}M$을 24시간 동안 처리하였을 때, 농도에 따른 ANG, VEGF 유전자 발현이 의미 있게 증가 하였다. 같은 방법으로, RSV $50{\mu}M$을 시간에 따라(0~48시간) 처리하여 실험하였다. 그 결과, RSV $50{\mu}M$을 24시간 동안 처리하였을 때 ANG, VEGF 유전자 발현이 가장 높게 증가하였고, ANG 단백질 분석에서도 동일한 결과를 얻었다. 또한, MTT assay를 이용한 세포 독성연구에서, RSV $50{\mu}M$의 농도에서는 영향을 미치지 않음을 관찰하여, 이를 최적의 조건으로 결정하였다. RSV가 처리된 세포에서 세포이동효과를 조사하기 위해 wound-healing assay를 수행하였다. RSV가 처리된 그룹에서 세포이동이 의미 있게 증가하였다. 따라서, 본 연구에는 RSV에 의해 ANG, VEGF의 발현이 증가했고, 이에 따라 세포이동이 향상됨을 관찰하였다.

• 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.

• Archives of Plastic Surgery
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• 제34권1호
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• pp.13-17
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• 2007

Purpose: To understand the pathogenesis of the disease that presents abnormally proliferated vascular endothelial cells, a model of DMH(1,2-dimethylhydrazine)-induced abnormal proliferation of HUVECs(Human Umbilical Vein Endothelial Cells) was made. We indirectly determined that Protein Kinase C(PKC) restricts the cellular proliferation and inhibits the manifestation of growth factor by using several inhibiting substances of the transmitter through our previous studies. Thereupon, we attempted to observe direct enzymatic activities of PKC and its correlation with the abnormal proliferation of vascular endothelial cells. Methods: $10^5$ HUVECs cells were applied to 6 individual well plates in three different groups; A control group cultured without treatment, a group concentrated with $0.75{\times}10^{-8}M$ DMH only, and a group treated with DMH & $5{\times}10^{-9}M$ Calphostin C, inhibitor of PKC. In analyzing the formation of intracellular PKC enzyme, protein separation was performed, and separated protein was quantitatively measured. PKC enzyme reaction was analyzed through Protein Kinase C Assay System (Promega, USA), and the results were analyzed according to Beer's law. Results: Enzymatic activity of PKC presented the highest in all reaction time of a group concentrated only with DMH, and the lowest in the control group. The group treated with DMH and the inhibitor revealed statistically lower enzymatic activity than group only with DMH in all reaction time, although higher than the control group. Conclusion: From the enzymatic aspect, most active and immediate reaction of the PKC was observed in the group concentrated with DMH only. The group treated with DMH & PKC inhibitor showed meaningful decrease. Accordingly, PKC holds a significant role in DMH-induced abnormal proliferation of vascular endothelial cells.