• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권4호
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• pp.330-336
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• 2001

Angiogenesis is an essential process for the growth, invasion and metastasis of cancer. However, it is uncertain that antiangiogenic effects can be a major treatment strategy of oral cancer. The aim of this study was to investigate whether thalidomide, which is known to be a potent inhibitor of angiogenesis, have inhibitory effect on the growth and antiangiogenic effects of oral squamous cell carcinoma(OSCC) xenografted in nude mice and whether antiangiogenesis of thalidomide can be included as a major treatment strategy of oral cancer. After human oral squamous cell carcinoma strain KB was subcutaneously implanted in 20 nude mice, the volume of tumor was measured every three days. When the tumor mass reached $75{\sim}100mm^3$, thalidomide(200mg/kg/d) was administered into 10 experimental nude mice and the same volume of distilled water was administered into 10 control nude mice and the tumor volume was measured every three days. The excised tumor masses on the 30th day after administration were frozen and processed for immunohistochemistry using vascular endothelial growth factor(VEGF) and CD31. We evaluated microvessel density and VEGF expression. The results were as follows ; 1. Thalidomide retarded the growth of human OSCC as compared with the control group, but it was not statistically significant. 2. A statistically significant lower microvessel density was observed in the thalidomide-treated group than in the control group(p<0.01) and thalidomide significantly reduced VEGF expression (p<0.01). Thalidomide exhibited significantly antiangiogenic effect, but did not inhibit the growth of human OSCC effectively. Antiangiogenic therapy of thalidomide alone is not likely to be effective in the treatment of human OSCC, but might be regarded as adjuvant chemotherapeutic strategy.

• 대한두경부종양학회지
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• 제27권1호
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• pp.59-65
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• 2011

Background and Objectives : Papillary thyroid carcinoma(PTC) frequently metastasize to the regional neck, however, lateral neck lymph node metastasis is less common. The aim of this study is to investigate clinical and immunohistochemical features of PTC with lateral LN metastasis, and determine the predictive factors for lateral LN metastases. Material and Methods : We undertook a retrospective study of 83 patients treated between January 2007 and December 2009 for PTC by thyroidectomy with or without lateral neck dissection. The following criteria were used to study the clinical predictive value of lateral LN. metastases : sex, age, tumor size, multifocality, extracapsular spread(ECS) and lymphovascular emboli. Immunohistochemical staining for VEGF-A, VEGF-C, Bax, Bcl-2, Cyclin D1, Cyclin E, $p27^{kip1}$ and $p57^{kip2}$ was performed, and quantified blindly by three pathologists who had no clinical information of the patients. Immunohistochemical expression was scored as high(>50% of cells stained) or low(0-49%). Results : With use of univariate and multivariate analysis, tumor size(>2cm) and ECS were independent correlates of lateral LN metastasis in PTC. Expression of VEGF-C, Bax, and Cyclin D1 in the PTC with lateral LN metastasis was scored higher than in PTC without lateral LN metastasis(p<0.05). Conclusion : The important risk factors for lateral LN metastasis in PTC are primary tumor size and the presence of ECS. And expression of VEGF-C, Bax and cyclin D1 may be considered of lateral LN metastatic potential in PTC.

• Journal of Korean Neurosurgical Society
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• 제40권6호
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• pp.428-433
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• 2006

Objective : We investigated the pattern of glucose uptake in meningiomas using $^{18}F$-fluoro-2-deoxy-D-glucose[FDG] PET/CT. It was hypothesized that the degree of glucose uptake in each tumor could predict the histologic grade. Methods : In 19 patients with meningiomas, the Ki-67 proliferative index, standardized uptake values[SUV] of FDG uptake, tumor to contralateral gray matter ratio[TGR] of SUV, tumor size, edema grade, vascular endothelial growth factor[VEGF] expression, histopathologic grade and the blood supply pattern were assessed. Results : Of the 19 meningiomas, 8 were meningothelial, 1 fibrous, 2 transitional, 1 psammomatous, 2 angiomatous, and 5 atypical. The tumor proliferative index of Ki-67, tumor size, and peritumoral edema were larger in the histopathologic grade-2 meninigiomas than in the grade-1 meningioma group. There were no significant differences in SUV and TGR between two groups. Tumor size and peritumoral edema were significantly larger in VEGF-positive tumors than in negative tumors. Conventional angiography was performed in 12 patients. Dural supply was noted predominantly in 2 patients. Four patients had mainly pial cortical supply patterns. In tumors with more pial supply, VEGF was more frequently positive. There was a significant relation between SUV and Ki-67 and between SUV and peritumoral edema. Conclusion : We found FOG uptake in meningiomas is associated with proliferative potential, however, no clear limits of SUV and TGR can be set to distinguish between grade-1 and grade-2 meningiomas, which makes the assessment of malignancy grade using PET scan metabolic imaging difficult in individual cases.

• Journal of Applied Biological Chemistry
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• 제65권4호
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• pp.269-275
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• 2022

자작나무(Betula platyphylla) 수피 추출물에는 생리활성을 보일 수 있는 다수의 terpenoids 물질이 포함되어 있고 염증반응을 완화시키는 치료제로 사용되어 왔다. 본 연구는 탈모예방 효과를 보일 수 있는 천연 물질을 확보하기 위해 자작나무를 여러 용매에서 추출 및 분리 정제하여 몇몇 분획을 획득하였다. 이를 사용하여 사람 모낭 모유두세포(HDP)에 대한 세포 독성 및 성장촉진 효과 그리고 β-catenin, VEGF, IGF1, Cyclin D의 발현변화와 5-α-reductase activity에 미치는 영향을 평가하였다. Ethyl acetate를 이용하여 분리한 4개의 분획 중 H3-2 분획은 알려진 유효물질인 ETB, LPO와 동등수준의 모낭 모유두세포(HDP)에 대한 성장 촉진 효과를 보였고 성장에 관여하는 주요인자들의 발현을 높이는 효과를 보였다. 또한, 5-α-reductase activity에 ETB, LPO가 큰 영향을 보이지 못한 반면 최종분획물인 H3은 5-α-reductase activity 감소활성이 있음을 확인할 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5189-5193
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• 2016

Objective: Dorema glabrum Fisch. & C.A. Mey is a perennial plant that has several curative properties. Anti-proliferative activity of seeds of this plant has been demonstrated in a mouse fibrosarcoma cell line. The aim of the present study was to evaluate cytotoxicity of D. glabrum root extracts in a human gastric adenocarcinoma (AGS) cell line and explore mechanisms of apoptosis induction, cell cycle arrest and altered gene expression in cancer cells. Materials and Methods: The MTT assay was used to evaluate IC50 values, EB/AO staining to analyze the mode of cell death, and flow cytometry to assess the cell cycle. Quantitative real-time polymerase chain reaction (qRT-PCR) amplification was performed with apoptosis and cell cycle-related gene primers, for cyclin D1, c-myc, survivin, VEGF, Bcl-2, Bax, and caspase-3 to determine alteration of gene expression. Results: Our results showed that n-hexane and chloroform extracts had greatest toxic effects on gastric cancer cells with IC50 values of $6.4{\mu}g/ml$ and $4.6{\mu}g/ml$, respectively, after 72 h. Cell cycle analysis revealed that the population of treated cells in the G1 phase was increased in comparison to controls. Cellular morphological changes indicated induction of apoptosis. In addition, mRNA expression levels of Bax and caspase-3 were increased, and of bcl-2 survivin, VEGF, c-myc and cyclin D1 were decreased. Conclusion: Our study results suggest that D. glabrum has cytotoxic effects on AGS cells, characterized by enhanced apoptosis, reduced cell viability and arrest of cell cycling.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.555-566
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• 2018

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and ${\beta}-catenin$; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

• 한국축산식품학회지
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• 제44권1호
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• pp.204-215
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• 2024

This study was designed to examine the effect of Lactilactobacillus curvatus LB-P9 on hair regeneration. The treatment of LB-P9 conditioned medium increased the proliferation of both hair follicle dermal papilla cells and hair germinal matrix cells (hGMCs). Moreover, the expression levels of hair growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 7 were significantly elevated in hGMCs co-cultured with LB-P9. After time-synchronized depilation, mice were orally administered with either 4×10⁷ colony forming unit (CFU) of LB-P9 (low dose) or 4×10⁸ CFU of LB-P9 (high dose), once daily for 4 weeks. Compared with the vehicle (phosphate-buffered saline)-administrated group, the LB-P9-treated groups exhibited accelerated hair regrowth rate and enhanced hair thickness in a dose-dependent manner. Supporting this observation, both hair follicle numbers and the dermal thickness in skin tissues of the LB-P9-treated groups were increased, compared to those of the vehicle-treated group. These results might be explained by the increased level of β-catenin and number of hair follicle stem cells (CD34⁺ CD49f⁺ cells) in the skin tissues of mice administered with LB-P9, compared to the vehicle-treated mice. Also, increased serum levels of hair growth factors such as VEGF and insulin-like growth factor-1, and superoxide dismutase were found in the LB-P9-treated groups, compared to those of the vehicle-treated group. Taken together, these results might demonstrate that the oral administration of LB-P9 promotes hair regeneration by the enhancement of dermal papilla proliferation through the stimulation of hair growth factor production.

• 통합자연과학논문집
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• 제10권3호
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• pp.141-147
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• 2017

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in angiogenesis, which is the formation of new blood vessels from pre-existing vessels. Consequently, blocking of the vascular endothelial growth factor receptor (VEGFR-2) by small molecule inhibitors leads to the inhibition of cancer induced angiogenesis. In this study, we performed a two dimensional quantitative structure activity relationship (2D-QSAR) study of 38 N-Phenyl-N'-{4-(4-quinolyloxy) phenyl} urea derivatives as VEGFR-2 inhibitors based on hologram quantitative structure-activity (HQSAR). The model developed showed reasonable $q^2=0.521$ and $r^2=0.932$ values indicating good predictive ability and reliability. The atomic contribution map analysis of most active compound (compound 7) indicates that hydrogen and oxygen atoms in the side chain of ring A and oxygen atom in side chain of ring C contributes positively to the activity of the compounds. The HQSAR model developed and the atomic contribution map can serve as a guideline in designing new compounds for VEGFR-2 inhibition.

• Annals of dermatology
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• 제30권6호
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• pp.653-661
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• 2018

Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6697-6701
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• 2013

Objective: To explore the inhibiting effect and mechanism of Endostar injection concomitant with cryoablation on lung adenocarcinoma A549 xenografts in nude mice. Materials and Methods: A total of 24 nude mice with subcutaneous xenografts of the A549 cell line were established and divided into 4 groups when the maximal diameters of tumors became 1 cm: control group, Endostar group, cryoablation group and combination group (Endostar concomitant with cryoablation). The nude mice were sacrificed after 21-days treatment, tumour tissues were removed to measure their volume, in situ test of TdT-mediated dUTP nick end labeling (TUNEL) was adopted to determine the cellular apoptosis around freezing injury zones, and immunohistochemical SP test was applied for the detection of micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression levels. Results: At 21-days after treatment, the growth velocities of control group, Endostar group, cryoablation group and combination group were $236.7{\pm}51.2%$, $220.0{\pm}30.6%$, $159.5{\pm}29.3%$ and $103.3{\pm}25.5%$ (P<0.01), while cellular apoptosis rates of tumors were $21.7{\pm}2.34%$, ($22.17{\pm}1.47$)%, $38.3{\pm}1.37%$ and $49.2{\pm}1.72%$, (P<0.01), respectively, according to the immunohistochemical test. MVD and VEGF expression levels in the combination group were both lower than in other groups (P<0.01), also being positively related (r=0.925, P<0.01). Conclusions: Endostar can significantly improve the inhibitory effects of cryoablation on xenografts of lung adenocarcinoma A549, and the mechanism is probably associated with its function as an inhibitor of tumour neo-angiogenesis through down-regulating VEGF expression.