• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.183-189
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• 2005

Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. The growth of tumor is dependent on angiogenesis. This study was aimed to determine the role of the VEGF expression and MVD(microvessel density) in salivary gland tumors and to analyze the correlation between the expression of VEGF/MVD, and clinical manifestation. Material and Methods: We analyzed the expression of VEGF and average MVD and neo-MVD in the 57 cases of salivary gland tumors by immunohistochemistry. Results: VEGF expression was higher in malignant tumors than in benign tumors. Average and neo-MVD were not different in benign tumor and malignant tumor. There was a tendency of positive correlation between VEGF expression and MVD but it was not statistically significant. Stage, T stage and recurrance rate were not correlated with VEGF expression, average-MVD and neo-MVD. Expression of VEGF, average-MVD and neo-MVD were significantly increased in Warthin's tumor compared with pleomorphic adenoma. Conclusion: Overexpression of VEGF has an important role in malignant salivary gland tumors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.2
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• pp.155-160
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• 2002

Oral squamous cell carcinoma (OSCC), the most common head and neck cancer, shows poor prognosis as a result of frequent local invasion and lymph node metastasis that is mediated by multiple proteolytic enzymes and angiogenesis. In recent reports, angiogenesis is known to play an important role in tumor invasion and metastasis. The purpose of this study was to determine the role of angiogenesis in OSCCs, particularly with respect to the invasive and the metastatic potential. The microvessel density (CD31) in 34 human OSCC cases were investigated by immunohistochemistry, and reviewed with respect to the invasiveness and the presence of lymph node metastasis and following results were obtained. The blood vessel density $(28.8{\pm}7.9)$ in the strong invasive cases were significantly higher than those $(23.3{\pm}6.9)$ in the weak invasive cases. (p<0.05) In the 14 cases with lymph node metastasis, the average blood vessel density was $28.5{\pm}9.6$. On the other hand, in the 20 cases without lymph node metastasis, the blood vessel density was $25.2{\pm}6.4$. The blood vessel density was not statistically related to lymph node metastasis. (p>0.05) These results suggest that angiogenesis may be related to the local invasion of OSCC and further research will be needed to investigate the possibility that antiangiogenic agent can be used as an anticancer agent for OSCC.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.6
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• pp.529-539
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• 2008

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.293-298
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• 2012

The purpose of this study was to investigate the modification of expression and functionality of the drug transporter P-glycoprotein (P-gp) by tumor necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) at the blood-brain barrier (BBB). We used immortalized human brain microvessel endothelial cells (iHBMEC) and primary human brain microvessel endothelial cells (pHBMEC) as in vitro BBB model. To investigate the change of p-gp expression, we carried out real time PCR analysis and Western blotting. To test the change of p-gp activity, we performed rhodamin123 (Rh123) accumulation study in the cells. In results of real time PCR analysis, the P-gp mRNA expression was increased by TNF-${\alpha}$ or IFN-${\gamma}$ treatment for 24 hr in both cell types. However, 48 hr treatment of TNF-${\alpha}$ or IFN-${\gamma}$ did not affect P-gp mRNA expression. In addition, co-treatment of TNF-${\alpha}$ and IFN-${\gamma}$ markedly increased the P-gp mRNA expression in both cells. TNF-${\alpha}$ or IFN-${\gamma}$ did not influence P-gp protein expression whatever the concentration of cytokines or duration of treatment in both cells. However, P-gp expression was increased after treatments of both cytokines together in iHBMEC cells only compared with untreated control. Furthermore, in both cell lines, TNF-${\alpha}$ or IFN-${\gamma}$ induced significant decrease of P-gp activity for 24 hr treatment. And, both cytokines combination treatment also decreased significantly P-gp activity. These results suggest that P-gp expression and function at the BBB is modulated by TNF-${\alpha}$ or/and IFN-${\gamma}$. Therefore, the distribution of P-gp depending drugs in the central nervous system can be modulated by neurological inflammatory diseases.

• IEIE Transactions on Smart Processing and Computing
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• v.6 no.2
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• pp.76-84
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• 2017

This paper presents an efficient method for generating spatiotemporal images in order to detect leukocyte motion in microvessels. Leveraging the constraint that leukocytes move along the contour line of the blood vessel wall, our proposed method efficiently generates spatiotemporal images for leukocyte motion detection. To that end, translational motion caused by in vivo movement is first removed by a template matching method. Second, the blood vessel region is detected by an automatic threshold selection method in order to binarize temporal variance images. Then, the contour of the blood vessel wall is expressed via B-spline function. Finally, using the detected blood vessel wall's contour as an initial curve, the plasma layer for the most accurate position is determined in order to find the spatial axis via snake, and the spatiotemporal images are generated. Experimental results show that the spatiotemporal images are generated effectively through comparison of each step with three images.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7651-7656
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• 2013

Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

• Applied Microscopy
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• v.35 no.4
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• pp.55-63
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• 2005

The characteristics of primary cultured rat brain microvessel endothelial cells (RBMECs) were studied using microscopy, immunohistochemistry and measuring of transendothelial electrical resistance (TER). The RBMECs formed a monolayer by $5{\sim}6$ days after plating and showed characteristics of whirling appearance. The TER increased until day 5 and decreased then. There was few immunoreaction with anti-GFAP, anti-GalC, anti-neurofilament 160/200 kD antibodies. So the contamination of astrocyte, oligodendrocyte, and neuron. could be ruled out.. Immunoreaction to vWF antigen was widespread througout the cytoplasm as Weibel-Palade granule. Immunoreaction to tight junction proteins, i.e. occludin, ZO-1, and ZO-2 was seen at cell contact. In summary, RBMECs isolated and cultured showed morphological, immunohistochemical and electrical characteristics of blood-brain barrier (BBB). The in vitro BBB model can be used in studying characteristics of in vivo BBB.

• Korean Journal of Bronchoesophagology
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• v.8 no.1
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• pp.35-41
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• 2002

Background and Objectives : Angiogenesis within malignant tumors has been considered to be essential for the growth and expansion of cancer cells, especially for solid tumors, and has been implicated in the overall growth and metastases of tumors. Such angiogenesis within tumors depends upon the secretion of vascular growth factor to allow the growth of newly formed vessels from peripheral tissue into the malignant tumor. %n, an exploration of the relations between cancer cells and vascular growth factors is absolutely critical to understanding the growth of malignant tumors. According to recent reports, vascular endothelial growth factor(VEGF) has been found to play a role in lymphatic metastases, tumor recurrence and survival in various human tumors. To evaluate the role of VEGF in head and neck squamous cell carcinoma(HNSCC) we performed this study. Materials and Methods : We examined the expression of VEGF and microvessel density in 39 HNSCC by immunohistochemistry and correlated them with various clinical data such as stage, cervical lymphatic metastasis, recurrence, and overall survival. Results : The expression of VEGF was not correlated with overall stage, T stage and N stage. There was no statistical correlation between the expression of VEGF and recurrence in the Primary site, cervical lymph node, and the distant metastases. There was no statistical correlation between the expression of VEGF and microvessel density. Conclusion : Based on these results, it is suggested that the expression of vascular endothelial growth factor is not a major prognostic factor for head and neck squamous cell carcinoma. Further studies are needed to evaluate significance of VEGF expression in head and neck squamous cell carcinoma.

• Proceedings of the Korea Contents Association Conference
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• 2011.05a
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• pp.201-202
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• 2011

본 연구에는 7.0T 동물용 자기공명영상장치를 이용하여 인간의 췌장암 세포인 CFPAC-1를 이종 이식한 쥐에서 자기공명영상을 획득하여 최적화된 검사 Protocol을 정립하며, 동물 실험에서 밝혀진 종양특성과 확산강조영상과의 비교 분석을 해보고 현성확산계수 영상이 췌장암 이종이식 모형의 종양 세포 내부 구조에 관하여 어떠한 정보를 제공 할 수 있는지 알아보고자 한다. 13마리의 쥐의 26개의 종양을 전형적으로 주입 후에 2~4주 뒤에 직경이 5~10mm가 되었을 때 imaged 하였으며, pathologic specimenm을 위해 sacrificed 하였다. isofluoran gas anesthesia를 이용하여 동물 마취 하였다. 사용된 장비로는 small-animal MR images (7.0-T)를 (Bruker BioSpin GmbH, Rheinstetten, Germany)이용하여 Fast T2-weighted 와 single-shot EPI DW image를 얻었다. 종양은 H&E 염색과 CD31와 VEGF에 대한 면역조직학 염색을 하여 종양의 cellularity와 microvessel density(MVD), 종양 내 괴사 정도를 평가하였다. CFPAC-1의 현성확산계수값은 $0.7327{\pm}0.1075{\pm}10^{-3}mm2/s$이였으며, 현성확산계수는 종양내 괴사 정도와 연관성을 보였다(R = 0.7417, p = 0.0001) 이처럼 현성확산계수는 종양 내 괴사 정도 등의 현미경적구조변화를 반영하는 대리인자로 사용될 수 있음을 확인하였다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.2
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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.