구강점막 편평상피세포암에서 림프관형성 유전자 발현

박영욱,김성곤,김소희,김한석,김민근,Park, Young-Wook,Kim, Seong-Gon,Kim, So-Hee,Kim, Han-Seok,Kim, Min-Keun 대한악안면성형재건외과학회 2009 Maxillofacial Plastic Reconstructive Surgery Vol.31 No.6

Background and Purpose: Vascular endothelial growth factor (VEGF)-C, VEGF-D and their tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. Oral mucosal squamous cell carcinoma (OMSCC) easily metastasizes to cervical lymph nodes, so we determined the expression levels of VEGF-C, VEGF-D and VEGFR-3 in oral squamous cell carcinoma. Materials and Methods: We performed Western blot analyses with 4 OMSCC cultured tumor cell lines (SCC9, KB, YD-10B, YD-38), and with 7 surgical specimens of OMSCC for the detection of VEGF-C, VEGF-D and VEGFR-3 proteins. Expression of VEGF-C mRNA as well as mRNA for VEGFR-3 in 4 OMSCC cell lines (KB, SCC-4, SCC-9, YD-10B) was investigated by RT-PCR. We also measured VEGFC/VEGF-D protein concentrations in the media and protein concentration of VEGFR-3 in cell lysates of 4 OMSCC cell lines (SCC9, KB, YD-10B, YD-38) using commerical ELISA kits. Finally, we performed immunoprecipitation for the detection of VEGF-C in cell lysates of 4 OMSCC cells (KB, SCC-4, SCC-9, YD-10B) and real-time RT-PCR for the quantification of VEGF-C mRNA. Results: In the result of Western blotting with cell lysates of 4 OMSCC cells, we could not detect the protein expression of VEGF-C, VEGF-D, and VEGFR-3. But, all tumor tissues demonstrated VEGF-C and VEGFR-3. VEGF-C mRNA was detected at various levels in 4 OMSCC cell lines. Moreover, OMSCC cells secreted VEGF-C, not VEGF-D and VEGFR-3 was also detected in cell lysates of OMSCC by ELISA. Immunoprecipitation and real-time RT-PCR revealed VEGF-C was also expressed in 4 OMSCC cell lines. Conclusion: Taken together, tumor cells of OMSCC secrete VEGF-C, not VEGF-D. And VEGFR-3 is expressed tumor cells as well as OMSCC tumor tissues, needs further study.

비소세포 폐암에서 C-erbB-2와 VEGF 발현에 대한 면역조직화학적 연구

신종욱 ( Jong Wook Shin ),하경원 ( Kyung Won Ha ),최재철 ( Jae Cheol Choi ),김재열 ( Jae Yeol Kim ),박인원 ( In Whon Park ),최병휘 ( Byoung Whui Choi ),유재형 ( Jae Hyung Yoo ) 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.62 No.1

배경 및 목적: 인체암에서 C-erbB-2의 과발현에 대한 광범위한 연구가 시행되고 있지만, 임상적 의의에 대해서는 논란의 대상이 되고 있다. 악성종양에서 신생혈관형성은 암의 진행에 필수적인 요소이다. 본 연구에서는 비소세포 폐암에서 C-erbB-2의 과발현의 의미, 암조직의 신생혈관형성에 중요한 역할을 하는 VEGF의 발현 및 두 표지자의 연관성을 연구하였다. 방법: 파라핀 포매된 95예의 비소세포 폐암조직을 이용하여 avidin-biotin complex 법에 의한 면역조직화학적 염색을 시행하였으며, 연구재료는 원발성 편평세포암종 60예 그리고 원발성 선암종 35예를 대상으로 하였다. 결과: 비소세포 폐암에서 선암종의 C-erbB-2의 과발현은 편평세포암종보다 의미 있게 높게 나타났다. 임상병기에 따른 C-erbB-2와 VEGF의 과발현은 진행암에서 증가하는 경향을 나타내었으나, 초기암과의 유의한 차이는 없었다. 선암종에서 C-erbB-2와 VEGF의 발현은 유의하게 상관성을 나타내었다. 결론: 비소세포 폐암에서 C-erbB-2의 과발현은 암의 유형에 따라 다르다는 것을 알 수 있었으며, C-erbB-2의 과발현이 높게 나타나는 선암종에서는 이 성적과 암세포의 VEGF의 발현이 상관성을 나타낸다는 것을 알 수 있었다. Background: Mutated or deregulated expression of C-erbB-2 causes this gene to function as a potent oncogene. Vascular endothelial growth factor (VEGF) is a crucial angiogenic molecule in lung cancer. Both C-erbB-2 and VEGF can promote growth, proliferation and metastasis in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate evaluate the relationship between the expressions of the C-erbB-2 and VEGF genes using immunohistochemistry. Materials and Methods: Ninety-five patients with NSCLC were involved (60 squamous cell carcinoma and 35 adenocarcinoma). The formalin-fixed paraffin embedded specimens were immunohistochemically stained for C-erbB-2 and VEGF using the avidin-biotin complex method. Results: Positive C-erbB-2 expression was observed more often in adenocarcinomas than squamous cell carcinomas (p<0.05). Although the immunohistochemical expressions of C-erbB-2 and VEGF in non-small-cell lung cancer showed increased tendencies at an advanced stage, the correlation between early and advanced cancers was insignificant. In adenocarcinomas, the expressions of VEGF and C-erbB-2 were significantly (p<0.05). Conclusion: The overexpression fo C-erbB-2 was significantly higher in adenocarcinomas than squamous cell carcinomas, and correlated with the expression of VEGF in adenocarcinomas of the lungs. (Tuberc Respir Dis 2007; 62: 43-50)

Decreased serum level and increased urinary excretion of vascular endothelial growth factor-C in patients with chronic kidney disease

( Sun Hee Kim ),( Yu Jin Jung ),( Kyung Pyo Kang ),( Sik Lee ),( Sung Kwang Park ),( Ju Hyung Lee ),( Nam Ho Kim ),( Won Kim ) 대한신장학회 2013 Kidney Research and Clinical Practice Vol.32 No.2

Background: Interstitial tonicity increases vascular endothelial growth factor-C (VEGF-C), a lymphangiogenic factor in salt-induced hypertension. Therefore, it can be assumed that changes of serum VEGF-C level may be associated with increasing blood pressure. However, there is no report about the changes of serum VEGF-C levels in patients with chronic kidney disease (CKD). The aims of this study were to investigate the changes of serum and urine VEGF-C levels in patients with CKD stage 3-4 and to evaluate the relationship between blood pressure and serum VEGF-C levels in the patients with CKD stage 5 and hemodialysis. Methods: Glomerular ?ltration rate (GFR) was assessed by the Modi?cation of Diet in Renal Disease equation. Blood pressure and VEGF-C levels (serum and urine) were measured by enzyme-linked immunosorbent assay (ELISA) in nine patients with stage 3-4 CKD, 41 hemodialysis patients, and eight healthy individuals. Results: The median serum level of VEGF-C in patients with stage 3-4 CKD and stage 5 hemodialysis signi?cantly decreased in comparison with healthy individuals. Urinary VEGF-C excretion increased in patients with stage 3-4 CKD compared with healthy control patients. For 41 hemodialysis patients, the serum level of VEGF-C in patients with stage 1 or stage 2 hypertension with hemodialysis did not signi?cantly increase when compared with prehypertension hemodialysis patients. Conclusion: We demonstrated that circulating levels of VEGF-C were decreased in patients with CKD, and the decrease of VEGF-C in patients with stage 3-4 CKD coincided with an increase in the urinary excretion of VEGF-C.

직장 결장암의 간전이 환자에서 VEGF-A, C, D 발현의 비교연구

전광식(Kwang-Sik Chun),이경하(Kyung-Ha Lee),송인상(In-Sang Song),김지연(Ji-Yeon Kim),김제룡(Je-Ryong Kim),안문상(Moon-Sang Ahn),이상일(Sang-Il Lee),박종현(Jong-Hyun Park),최송이(Song-E Choi),강대영(Dae-Young Kang),송규상(Kyu-Sang Son 대한외과학회 2009 Annals of Surgical Treatment and Research(ASRT) Vol.76 No.5

Purpose: We aimed to investigate the correlations between expressions of angiogenic cytokines VEGF-A, C, D of primary colorectal cancer and liver metastasis. Methods: We examined paraffin-embedded primary colorectal cancer tissue from 45 patients who had liver resection due to colorectal liver metastasis (metastasis group) and 37 patients who had surgical resection due to colorectal cancer only (control group). In the control group, local recurrence and distant metastasis had not occurred. Immunohistochemical staining for VEGF-A, C and D was performed. We analysed the correlations between expression of VEGF-A, C and D in primary colorectal cancer tissues and clinicopathologic parameters. Results: VEGF-A expressions of primary colorectal carcinoma were not different between the two groups. VEGF-C was more frequently expressed in the metastasis group (P=0.008) but VEGF-D was more expressed in the control group (P=0.003). Patients with VEGF-C negative and VEGF-D positive expression were predominant in the control group (P=0.020). Tumor location, T stage, lymph node metastasis and tumor differentiation were not related with the expressions of VEGF-A, C, D but only preoperative CEA was positively correlated with VEGF-A and C expression. Conclusion: Expressions of VEGF-C in primary tumor were more frequent in metastatic colorectal cancer and expressions of VEGF-D were more frequent in nonmetastatic colorectal cancer. More large-scale prospective studies for VEGF-C and D expression in colorectal cancer are necessary.

VEGF-C and VEGF-D Expression and its Correlation with Lymph Node Metastasis in Esophageal Squamous Cell Cancer Tissue

Yang, Zeng,Wang, Yong-Gang,Su, Kai Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: To explore vascular endothelial growth factor C (VEGF-C) and VEGF-D expression and its correlation with lymph node metastasis in esophageal squamous cell cancer (ESCC) tissue. Materials and Methods: Immunohistochemical methods were applied to detect the levels of VEGF-C and VEGF-D expression in 64 surgicall removal ESCC tissues, tissues adjacent to cancer and normal tissues, and the relationship between VEGF-C and VEGF-D expression and lymph node metastasis was analyzed. Results: Both VEGF-C and VEGF-D were expressed by varying degrees in esophageal cancer tissue, the tissue adjacent to cancer and normal tissue, and the positive expression rate went down successively. The positive expression rates of VEGF-C (59.4%) and VEGF-D (43.8%) in esophageal cancer tissue were significantly higher than in the tissue adjacent to cancer (34.4%, 15.6%) and normal tissue (20.3%, 12.5%), respectively, in which significant differences were manifested (p<0.01). Positive expression rates of VEGF-C and VEGF-D in esophageal cancers with lymph node metastasis were markedly higher than without such metastasis (p<0.01), while those in the tissue with TNM staging I~II were markedly lower than that with TNM staging III~IV (p<0.01). Conclusions: Both VEGF-C and VEGF-D are highly expressed in ESCC tissue, which may be related to the lymph node metastasis of cancer cells. Hence, VEGF-C and VEGF-D can be clinically considered as important reference indexes of lymph node metastasis in esophageal cancer.

점막하 침윤 조기위암에서 Vascular Endothelial Growth Factor (VEGF)-C와 VEGF-D의 발현

김정구(Jeong Goo Kim),최명규(Myung Gyu Choi),박원상(Won Sang Park),이상철(Sang Chul Lee),이동호(Dong Ho Lee),유영경(Young Kyoung You),안창준(Chang Joon Ahn),박조현(Cho Hyun Park) 대한외과학회 2008 Annals of Surgical Treatment and Research(ASRT) Vol.74 No.1

Purpose: Vascular endothelial growth factor (VEGF)-C and VEGF-D are considered novel growth factors that potentially induce lymphangiogenesis and hyperplasia of lymphatic vessels. The aim of this study was to investigate whether the expressions of VEGF-C and VEGF-D are associated with the clinicophathologic factors, and particularly lymphatic invasion and lymph node metastasis, in early gastric cancers that’s invaded the submucosa. Methods: Using immunohistochemical staining, we studied the VEGF-C and VEGF-D expressions in the gastric cancer specimens from 83 patients who underwent curative gastrectomy. Results: The VEGF-C and VEGF-D immunoreactivity was mainly located in the cytoplasm of the tumor cells. There was a positive VEGF-C expression in 27 of 83 cases (32.5%). The VEGF-D positivity rate was lower than the VEGF-C positivity rate. VEGF-D was positive in 20 of 83 cases (24.0%). A VEGF-C positive expression was associated with lymphatic invasion (P=0.018) and lymph node metastasis (P=0.001). However, the expression of VEGF-D had no correlation with any of the clinicopathologic factors, including lymphatic invasion and lymph node metastasis. Conclusion: The VEGF-C expression may have a role in lymph node metastasis of gastric cancer cells. The VEGF-C expression in tumor specimens may be a reliable marker for lymph node metastasis of early gastric cancer that’s invaded the submucosa.

점막하 침윤 조기위암 환자에서 VEGF-C와 COX-2 발현의 임상적 의의

조윤정,이정의,이관주,박조현,박승만,전해명,안창준,김정구,이동호,이상철 대한위암학회 2009 Journal of gastric cancer Vol.9 No.3

목적: Vascular endothelial growth factor (VEGF)-C와 -D 및 Cyclooxygenase (COX)-2는 위암에서 림프절 전이와 연관이 있다고 알려져 있다. 이에 저자들은 점막하 침윤 조기위암에서 VEGF-C와 -D 및 COX-2의 발현과 림프절 전이 등을 포함하는 다양한 임상병리학적 인자와의 관련성을 알아보고자 하였다. 대상 및 방법: 1991년 1월부터 2007년 10월까지 본원에서 점막하 침윤 조기위암으로 수술을 시행 받은 85명의 환자를 대상으로 VEGF-C, -D 및 COX-2와 VEGF-C에 대한 면역 조직화학 염색을 시행하였다. 염색의 결과에 따라 환자군을 나누어 다양한 임상병리학적 인자와의 연관성을 조사하였고, 또 이 세 가지 인자들 상호 간의 연관 관계를 분석하였다. 결과: 전체 85명의 환자 중 16명이 림프절 전이가 있었다(18.8%). VEGF-C는 34.1% VEGF-D는 22.3% 그리고 COX-2는 37.6%가 양성으로 판정되었다. 이 중 VEGF-C와 COX-2 모두 림프절 전이와 유의한 상관관계를 보였고(P<0.001, P=0.023), VEGF-D와 연관성을 보이는 인자는 확인하지 못하였다. 또 VEGF-C와 COX-2의 발현은 밀접한 상관관계를 보였다(P=0.001). 결론: 점막하 침윤 조기위암에서 VEGF-C와 COX-2는 림프절 전이와 연관이 있고, 따라서 이 두 인자가 점막하 침윤조기위암의 림프절 전이를 예측하는 인자로서의 가능성이 있다고 할 수 있겠다.

조기위암에서 E-cadherin, VEGF-C, VEGF-D의 발현과 Cytokeratin 18로 면역화학염색 한 림프절 전이와의 연관성

김대훈,윤효영,송영진,류동희,민인철,성노현,이상억 대한위암학회 2008 Journal of gastric cancer Vol.8 No.2

목적: VEGF-C와 VEGF-D는 맥관형성성 인자이고, E-cadherin 의 비정상 발현은 위암의 진행에 중요한 역할을 한다. 이 연구의 목적은 조기위암에서 E-cadherin, VEGF-C, -D 그리고 cytokeratin 18번을 이용하여 정확하게 측정된 림프절 전이 와의 연관성을 연구하는데 있다. 대상 및 방법: 1997년 3월부터 2002년 12월까지 49명의 조 기 위암환자들을 대상으로 E-cadherin, VEGF-C와 VEGF-D 면 역화학염색을 시행하였다. 림프절 전이를 정확하게 측정하 기 위하여 49명 환자들의 1,562개의 림프절을 cytokertin 18 을 사용하여 재검사 하였다. 결과: 11 (0.7%)개의 림프절이 12.2% (n=6)의 환자들로부터 새롭게 발견되었다. 정확한 림프절 전이는 점막암에서 3.6%였고, 점막하암에서 38.1%였다. 병기 이동은 3명(6.1%) 의 환자에서 관찰되었다. E-cadherin의 비정상 발현은 36.7% 에서 발견되었고, VEGF-C와 VEGF-D의 발현은 각각 16.3%와 36.7%에서 관찰되었다. E-cadherin의 비정상 발현은 종양의 분화도(P<0.0103)와 Lauren 분류(P<0.0001)와 뚜렷한 연관 성이 있었다. VEGF-C와 VEGF-D는 조기위암에서 림프절 전 이를 포함한 임상병리학적 연관성이 없었다. 그러나 E-cadheirn이 비정상 발현되고 VEGF-C 또는 VEGF-D의 발현이 동 반되는 환자들에서 림프절 전이의 빈도가 높았다(P=0.0031). 결론: 본 연구에서 조기위암에서 림프절 전이와 VEGF-C, VEGF-D의 발현과의 관계를 증명할 수 없었다. 하지만 E-cadherin이 비정상 발현을 하면서 VEGF-C 또는 VEGF-D의 발현 을 동반할 경우 림프절 전이와 연관성이 있었다.

Expression of Vascular Endothelial Growth Factor-C (VEGF-C) and Its Receptor (VEGFR-3) in the Glial Reaction Elicited by Human Mesenchymal Stem Cell Engraftment in the Normal Rat Brain

Shin, Yoo-Jin,Riew, Tae-Ryong,Park, Joo-Hee,Pak, Ha-Jin,Lee, Mun-Yong SAGE Publications 2015 The Journal of histochemistry and cytochemistry Vol.63 No.3

<P>To determine whether vascular endothelial growth factor-C (VEGF-C) and its receptor (VEGFR-3) are involved in the glial reaction elicited by transplanted mesenchymal stem cells (MSCs), we examined the cellular localization of VEGF-C and VEGFR-3 proteins in the striatum of adult normal rats that received bone marrow-derived human MSCs. The MSC grafts were infiltrated with activated microglia/macrophages and astrocytes over a 2-week period post-transplantation, which appeared to parallel the loss of transplanted MSCs. VEGF-C/VEGFR-3 was expressed in activated microglia/macrophages recruited to the graft site, where the induction of VEGF-C protein was rather late compared with that of its receptor. VEGF-C protein was absent or very weak on day 3, whereas VEGFR-3 immunoreactivity was evident within the first three days. Furthermore, within three days, VEGF-C could be detected in the brain macrophages localized immediately adjacent to the needle track. At the same time, almost all the brain macrophages in both regions expressed VEGFR-3. Reactive astrocytes at the graft site expressed VEGFR-3, but not VEGF-C. These data demonstrated the characteristic time- and cell-dependent expression patterns for VEGF-C and VEGFR-3 within the engrafted brain tissue, suggesting that they may contribute to neuroinflammation in MSC transplantation, possibly through the recruitment and/or activation of microglia/macrophages and astrogliosis.</P>

갑상선유두상암 환자에서 말초혈액의 종양표지자와 임상 소견과의 상관관계

오세준,이영옥,이병주,이진춘,왕수건,김용기,김인주,손석만 한국레이저가공학회 2008 한국레이저가공학회 학술대회 논문집 Vol. No.

Background and Objectives : Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are involved in the pathogenesis and development of thyroid cancer. The purpose of this study was to find the correlation between serum VEGF, VEGF-C, MMP-9, EGF, HGF and clinicopathologic factors. Subjects and Method : Using enzyme linked immunosorbent assay (ELISA) kit, 64 patients with thyroid papillary cancer, 15 benign thyroid mass patients and 14 healthy normal control were analyzed to investigate the expression of human VEGF, VEGF-C, MMP-9, EGF and HGF. Results : There were no significant differences in the serum levels of VEGF, VEGFC, MMP-9, TGF, EGF between papillary thyroid cancer group and the benign thyroid tumor group. Levels of VEGF and MMP9 appeared higher in lateral cervical lymph node metastasis than NO lymph node metastasis or only cervical component lymph node metastasis. But, the serum VEGF-C level was significantly related with tumor size, T stage, extrathyroidal extension and lateral cervical lymph node metastasis (p=0.043). Conclusion : VEGF, VEGF-C, MMP-9, HGF and EGF could not be used as a diagnostic tool for differentiating malignancy from benign thyroid disease. Serum VEGF, VEGF-C and MMP-9 levels were correlated with lateral cervical lymph node metastasis of papillary thyroid cancer. Consequently, this results suggests that they may serve as preoperative supplementary marker for determining the extent of papillary thyroid cancer surgery. Also, serum VEGF-C levels were correlated with some prognostic factors of papillary thyroid cancer.