• Korean Journal of Head & Neck Oncology
• /
• v.14 no.1
• /
• pp.70-75
• /
• 1998

Tumor growth and metastasis depends on angiogenesis. Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells in vitro and promotes neoangiogenesis in vivo. Objective: Follicular thyroid cancers(FTC) are a vascular tumor and traditionally metastasize via blood vessels. Likely other cancers, angiogenesis may playa important role in FTC. We, therefore, investigated the expression of VEGF and microvascular density by immunohistochemistry in FTC and follicular adenoma(FA). Materials and Methods: Findings of immunohistochemical stainings for VEGF and CD31 were measured by grading scale from +1 to 4+(strongest) and by counting the stained microvessels in 14 FTCs and 14 FAs. Results: 1) Expression of VEGF. a) FTCs have stronger expression than FAs in areas of tumor adjacent to capsule($mean{\pm}SD\:\;3.2{\pm}0.9\;vs\;2.0{\pm}0.9$, p<0.01) and in central area($2.3{\pm}0.7\;vs\;1.3{\pm}0.6$, p<0.01). b) The VEGF expression of capsular area in FTCs are higher than that of central area(p<0.05). 2) Microvascular density by CD31. a) FTCs have more microvessels than FAs in areas of adjacent to capsule($78.9{\pm}27.3\;vs\;38.7{\pm}15.6$, p<0.01) and in central area($75.5{\pm}23.3\;vs\;27.8{\pm}10.7$, p<0.01). b) In FTCs, the number of microvessels of capsular area are more than that of central tumor area, but not significant statistically(p>0.05). Conclusion: The higher expression of VEGF and microvascular density in FTC suggests angiogenesis plays an important role in progression of FTC.

• Journal of Chest Surgery
• /
• v.33 no.4
• /
• pp.277-284
• /
• 2000

Background: Coronary artery bypases grafting in the old aged is associated with high mortality and morbidity, and it is difficult to perform if the coronary artery is diffusely disease. Recently it has been known that platelet derived growth factor(PDGF), especially PDGF-BB, stimulates angiogenesis. Material and Method: New Zealand white rabbit were used. In an attempt to achieve effevtive cardiac revasculatrization without vascular anastmosis, we divided into three groups(group I : Left anterior descending artery(LAD) was occluded by ligature, group II : Bilateral internal mammary vascular pedicles were dissected and implanted into myocardium, group III : The vascular pedicles were implanted into myocardium and PDGF-BB was injected into the myocardial tissue). Two weeks after IMA implantation, the proximal region of implanted LAD was ligated. Four days after LAD ligation angiogram, triphenyl tetrazolium chloride(TTD) staining and hematoxylin eosin staining were performed. Result: 1. Survival rate in group II was significantly higher than that in group I (P<0.05), and survival rate in group III was signficantly higher than that in group II(53% vs 93%, P<0.01). 2. There were significant differences in the ratio of area of necrosis to area at risk between group I and group II, and between group II and group III (P<0.01). 3. Microangiogram for angiogenic response revealed wide area of extensive revascularization with patent vessels in group III. 4. Histologic findings of three groups showed that polymorphonuclear leukocyte infiltration was minimal in group II and none in group III. Conclusion: PDGF-BB can establish functinal cardiac revasculatization through systemic vessels implanted directly into the myocardium.

• Korean Journal of Clinical Laboratory Science
• /
• v.37 no.3
• /
• pp.197-206
• /
• 2005

To determine the correlation between mast cells(MCs) and neoangiogenesis in the growth and progression of cervical cancer, we investigated mast cell density(MCD), microvessel density(MVD) and the expression of vascular epithelial growth factor(VEGF) in cervical intraepithelial neoplasia and invasive suqamous cell carcinoma of the uterine cervix. Forty-five cervical intraepithelial neoplasia(CIN I, II and III), 15 microinvasive carcinomas, 15 invasive squamous cell carcinomas and 20 normal cervical epithelia were included in this study. MCs were stained with anti-c-Kit antibody and alcian blue, microvessels with anti-factor VIII antibody and VEGF with anti-VEGF antibody. The adjacent fields of both normal and neoplastic epithelium were used for counting MCs and microvessels. Computerized image analysis was used to evaluate MCD and MVD. MCD and MVD were the mean numbers per $1mm^2$ counted in 5-10 high and low power fields respectively. In both c-Kit and alcian blue stained sections, MCD progressively increased along the continuum from CIN I to invasive squamous cell carcinoma(p<0.001). MVD increased significantly with cervical neoplasia progression, from CIN to invasive squamous cell carcinoma (p<0.001). In double c-Kit and Factor VIII-stained sections, MCs were mainly present in the areas adjacent to newly formed blood vessels. However, there were no significant differences in MCD and MVD between normal epithelum and CIN I. A strong correlation was also observed between MCD and MVD. In double VEGF and alcian blue-stained sections, VEGF was expressed in only MCs. Strong VEGF-positive MCs were particularly abundant around the tumorous region. Our results suggest that MCs may upregulate neoangiogenesis by VGEF secretion in the development and progression of cervical neoplasia.

• Clinical and Experimental Pediatrics
• /
• v.48 no.8
• /
• pp.886-893
• /
• 2005

Purpose : Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin(IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor(VEGF)-induced tube formation of endothelial cells in vitro on Matrigel assay. Methods : Human umbilical vein endothelial cells(HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents : VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. Results : IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. Conclusion : We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.

• Archives of Plastic Surgery
• /
• v.37 no.1
• /
• pp.7-11
• /
• 2010

Purpose: Vascular endothelial growth factor (VEGF) is known as a growth factor of endothelium and fibroblast. The purpose is to know the VEGF effects on fibroblast proliferation and fibroblast's notch receptor expression. Methods: CCD-986sk fibroblast was purchased from the Korean Cell Bank and was used in XTT assay for proliferation and wound healing assay for migration. Immunofluorescent (IF) staining and western blotting were used in testing notch expression of fibroblast. Semiquantitative RT-PCR was used in checking notch 1 mRNA production by fibroblast. Student-t test was used for analyzing results. Results: Cell proliferation assay using XTT showed significant higher proliferation in VEGF treated fibroblast, $2.324{\pm}0.0026$ vs. $2.463{\pm}0.017$ (p=0.002). Wound healing assay showed longer migration in VEGF treated fibroblast (p=0.062). The fluorescence was brighter in VEGF treated cells of notch 1 IF staining. Notch 1 expressions and mRNA productions increased more in VEGF treated cells. Conclusion: VEGF stimulates fibroblast to proliferate, migrate and to express Notch 1 simultaneously. Notch receptor could be related to VEGF mediated wound healing.

• Journal of Life Science
• /
• v.14 no.1
• /
• pp.154-162
• /
• 2004

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated and at transcriptional level by external stimuli. Previously, we found that phorbol 12-myristate 13-acetate (PMA) suppressed TSP-1 expression in porcine aortic endothelial (PAE) cell, but enhanced in hepatoma cell line, Hep 3B cell. A region between -767 and -723 on the tsp-1 promoter was defined as a responsive site to the suppression in PAE cell. eased on the previous results, the molecular mechanism of TSP-1 expression was determined by characterizing interactions between cis-elements and trans-factors using three overlapped oligonucleotide probes, oligo a-1 (from -767 to -738), a-2 (-759 to -730) and a-3 (-752 to -723). The results from electromobility shift assay showed that PMA-induced suppression of TSP-1 transcription in PAE cell might be caused via a negative regulator binding to the region from -752 to -730 and additionally generated by lacking two positive regulators binding to the sites from -767 to -760 and from -752 to -730. Especially, PMA enhanced the binding ability of the negative regulator to the site from -752 to -730 in PAE cell, but anti-c-Jun did not affected its binding ability.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.35 no.2
• /
• pp.66-73
• /
• 2009

Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.

• The korean journal of orthodontics
• /
• v.27 no.5 s.64
• /
• pp.683-696
• /
• 1997

Recently several growth factors such as $TGF-{\beta}1$, $TGF-{\beta}1$, PDGF, bFGF are known to play an important role in scar formation following adult tissue injury. But there is little known about the role of growth factors in fetal tissue healing without scar formation. Therefore the purpose of this study is to investigate the distribution of growth factors which we involved with scar formation in the artificially created cleft lip wound healing of fetuses. The author had undergone hysterotomy and created cleft lip-like defects on fetuses of New Zealand White Rabbit in mid-third trimester (24 days). Fetuses were divided into 3 groups (the repaired group, the unrepaired group and the sham-operated control group). At 1, 2, 3, 5, 7 days after procedure, the repaired, the unrepaired and the control groups were obtained by Caeserean section. After documenting the viability of fetuses, fetuses were photographed to compare size and facial morphology and sectioned for histological examination by H & E stain and spatial and temporal deposition of $TGF-{\beta}1$, $TGF-{\beta}2$, PDGF, bFGF by immunohistochemical method. The findings are summarized as follows 1. There were lack of inflammation and scar formation and neovascularity in the repaired and the unrepaired group during experimental periods. 2. The reepithelialization of the unrepaired group was slower than that of repaired group. 3. There were no differences of distribution of bFGF in the control, the repaired and the unrepaired group. 4. PDGF was increased at post-op. first and second day and decreased after post-op. third day. Eventually, there were no differences in the control, the repaired and the unrepaired group. 5. $TGF-{\beta}1$ and $TGF-{\beta}2$ were slightly increased at post-op. first and second day and decreased after post-op. third day. Eventually there were no differences in the control, the repaired and the unrepaired group. And $TGF-{\beta}2$ is more densely stained than $TGF-{\beta}1$.

• Journal of Life Science
• /
• v.28 no.8
• /
• pp.992-998
• /
• 2018

Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

• The korean journal of orthodontics
• /
• v.25 no.1 s.48
• /
• pp.31-42
• /
• 1995

This study was designed to evaluate the expression of growth factor in periodontal tissue during the experimental movement of rat incisors by LSAB(Labelled streptavidine Biotin) immunohistochemical staining for EGF(Epidermal growth factor). 23 Sprague-Dawley rats were divided into a control group(3rats) and experimental groups(20rats), where a force(75g) from helical springs across the maxillary incisors was applied. Experimental groups were sacrificed at 12 hours, 1, 4, 7 and 14 days, after force application, respectively. And Tissue slides of control and experimental groups were studied immunohistochemically and histologically. The results were as follows : 1. In 14days after force application, periodontal fibers were strectched on the tension side, and compressed In pressure side of all experimental groups, and the arrangement of periodontal fibers was not recovered yet. 2. The degree of EGF expression in control group was strongly positive in the oral epithelium, predentin, capillaries in pulp and periodontal spaces. But osteoblasts and osteoclasts were stained mildly positive. 3. EGF expression was mild and diffuse in 12 hours, 1, 4 and 7 days of experimental groups and was not significantly different between the tension and pressure sides. 4. The degree of EGF expression in the 14-day experimental group was higher than any other group. And the tension side showed a more positive EGF expression than the pressure side. The apical area revealed a more positive EGF expression than the cervical area.