• 대한치과보철학회지
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• 제51권2호
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• pp.82-89
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• 2013

연구 목적: 본 연구는 양극산화 임플란트에 골형성단백질과 혈관내피세포성장인자를 코팅한 임플란트를 토끼의 경골에 식립하여 골과 임플란트 계면의 골유착 향상의 가능성을 평가하고자 시행하였다. 연구 재료 및 방법: 6마리의 토끼 양측 경골에 코팅을 하지 않은 양극 산화 임플란트(대조군)와 골형성단백질과 혈관내피세포성장인자를 코팅한 임플란트(실험군)을 각각 한쪽에 2개씩 식립하였다, 토끼는 2주, 8주에 각각 3마리씩 희생하였고 전체 식립된 임플란트는 24개이었다. 각 시기별, 그룹별 임플란트 수는 각각 6개씩이었다. 임플란트안정지수(resonance frequency analysis (RFA)), 회전 제거력(Removable torque measurement (RTQ))을 희생 시기에 측정하였다. 독립표본 t-test (SPSS Ver. 15.0, Chicago, USA)을 이용하여 2주, 8주에서 대조군과 실험군의 차이를 비교 분석하고, 유의수준95%에서 통계적으로 검정하였다. 결과:대조군과 실험군 모두 8주에서 우수한 골유착을 보였다. 특히 실험군에서 8주에 ISQ, RTQ 값 모두 대조군과 비교하여 우수한 값을 나타내었다 (P<.05). 하지만 2주에서는 두군 사이에 통계적 유의성을 보이지 않았다(P>.05). 결론: 골형성 단백질과 혈관내피세포성장인자를 임플란트 표면에 코팅하여 식립하는 것은 치유의 후반기에 골유착을 증대하는 것으로 사료된다.

• Journal of Chest Surgery
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• 제33권6호
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• pp.494-501
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• 2000

Background: Transmyocardial laser revascularization(TMLR) for revascularizing ischemic myocardium in patients was originally based on the assumption that laser channels remain their patency much longer. But recent studies show that laser channels did not remain open and that TMLR could achieve treatment benefits without long-term channel patency. The angiongencesis is currently thought to be induced by non-specific inflammatory response to mechanical tissue injury. This study is to evaluate hypothesis that various transmyocaridal mechanical revascularization(TMMR) may induce the angiogenic responses similar to that seen with TMLR, and transmyocaridal polymer stent revascularization(TMSR), the polymer stent in the myocardial tissue is hydrolyzed in 2 weeks, may enhance the non-specific inflammatory reaction resulting angiogenesis. Furthermore, polymer myocaridal stent channels remain long-term patency. Material and Method: Eight domestic pigs underwent ligation of the proximal circumflex artery, and 2 weeks later they were randomized to undergo transmycardial acupunctural revascularization (TMPR, Group I) of the left lateral wall with 18-G needle(n=2), to undergo transmyocardial (TMDR, Group II) with industrial 2mm steel drill(n=2), to undergo transmyocardial polymer stent revascularization (TMSR, Group III) after drilling the infarcted myocardium(n=2), the stent is poly(lactic acid-co-glycolic acid), which is self-degradated in the myocardium, and to a control group the ischemic zone was unterated(n=2). All the pigs were sacrificed after 4 weeks TMMR. Sections from the ischemic zone were submitted for vascular endothelial growth factor (VEGF) ELISA and histology. Result: There were makedly increase in the VEGF immunoassay in the ischemic zone of the TMMR group compared to the ischemic zone of the control group(control: each 30.85 and 43.15pg/mg protein, TMPR: each 44.14 and 68.61 pg/mg protein, TMDR: each 65.92 and 78.65 pg/mg protein, TMSR: each 177.39 and 168.87 pg/mg protein). TMSR channels caused greatest VEGF expression than channels made by other group and the polymer stent channels remained vacuole after 4 weeks. Conclusion: Transmyocardial polymer stent revascularization promoted the most angiogenci response by the VEGF immunoassay, although our study did not show the statistical significancy. The channels remained but the flow patency was not verified. Transmyocardial polymer stent revascularization (TMSR) is desirable in future experimental trials and in view of the significant cost implications comparable to that of laser.

• 대한화장품학회지
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• 제41권4호
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• pp.401-411
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• 2015

본 연구에서는 피부재생 화장품 소재로 활용하고자 저분자화 시킨 Polydeoxynucleotide (PDRN)의 창상 치유 효과를 조사하였다. 이를 위하여 연어 정소 유래 PDRN 단백질 제거공정, 내독소 제거공정을 거쳐 순수분리 정제하였고 분자량 저감공정을 거쳐 기존 PDRN 보다 피부 침투율을 높인 고순도 PDRN을 제조하였다. 상처 치료 과정 중 PDRN 처리에 의한 효능을 평가하기 위해 sprague-dawley rats (SD)의 배부에 bioxy punch를 이용한 4개의 창상을 유발하고, 시료를 포함한 총 5종의 실험시료를 마리당 $500{\mu}L$씩 도포한 후 7일 간격으로 4주간 피부조직 변화를 관찰하였다. 상처에 PDRN을 도포한 후, 절개된 상처의 표피화와 수축이 더 빨라졌고, 창상면적에 있어서 PDRN의 도포는 양성대조군인 $Fucidin^{(R)}$ 도포군과 비교하여 유의하게 줄어들었다. 염색한 조직의 현미경 관찰 결과에서는 양성대조군이 가장 빠르게 재상피화가 이루어졌으며, 그 다음으로는 PH군, PD군, HA군으로 교원질 재합성 및 형성 수준을 보였다. 또한, 병변의 형질전환성장인자($TGF-{\beta}$) 및 혈관 내피성장인자(VEGF) 등의 성장인자에서도 염색 조직의 결과와 유사하게 나타났다. 이러한 결과를 종합하여 볼때, 저분자화된 PDRN은 창상에 치료효과가 있다고 판단되며, 화장품 및 의료산업 분야의 기능성 소재로 활용 가능할 것으로 판단되어 진다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3977-3982
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• 2012

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

• Molecules and Cells
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• 제45권12호
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• pp.935-949
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• 2022

Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of β-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)- related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4571-4576
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• 2015

Background: To investigate the inhibitory effect and the underlying mechanism of triptolide on cultured human endometrial carcinoma HEC-1B cells and corresponding xenograft. Materials and Methods: For in vitro studies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cell cycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivo studies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, then the tumor-bearing mice were treated with high, medium, and low-dose ($8{\mu}g$, $4{\mu}g$ and $2{\mu}g/day$) triptolide or cisplatin at $40{\mu}g/day$ or normal saline as control. The mice were treated for 10-15 days, during which body weight of the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growth factor (VEGF) was analyzed by SABC immunohistochemistry. Results: Cell growth was significantly inhibited by triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated that triptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed that low concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higher concentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosis of the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%); high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared to normal saline control (P<0.05). Conclusions: triptolide inhibits HEC-1B cell growth both in vitro and in mouse xenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involve induction of tumor cell apoptosis and inhibition of tumor angiogenesis.

• Archives of Plastic Surgery
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• 제42권1호
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• pp.11-19
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• 2015

Background Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. $K^+$ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether $K^+$ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing. Methods The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether $K^+$ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot. Results The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors. Conclusions Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the $K^+$ ion channel.

• Nuclear Medicine and Molecular Imaging
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• 제42권4호
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• pp.307-313
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• 2008

목적: 혈관내피성장인자(VEGF)와 그 수용체는 종양의 성장과 전이에 매우 중요한 역할을 한다 3개의 수용체가 알려져 있는데 그 중에서도 VEGFR2 (Flk-1/KDR)가 종양 angiogenesis에 매우 밀접하게 관련한 것으로 알려져 있다. 본 연구에서는 마우스 Flk-1 항체로 알려진 DC101에 I-131을 표지하여 매우 공격적인 종양으로 알려진 흑색 종의 치료 정도를 확인해 보고자 하였다. 방법: 하이브리도마 세포에서 Flk-1 항체인 DC101을 분리하여 western blot, ELISA, maldi-tof 방법을 이용하여 순도를 확인하고 항체 에 chloramin T를 이용하여 I-131을 표지하였다. 누드마우스에 B16F10세포를 주사하여 흑색종 모델을 만들고 평균 $200-250\;mm^3$으로 키워 $^{131}I$-DC101을 주사하여 영상과 시간별 장기섭취율(%ID/g)을 비교하고, 종양내 Flk-1 발현을 확인하기 위하여 면역염색 등을 시행하였다. 흑색종 동물모델을 5개 군으로 나누어 각각 치료를 시행하였다. 1군은 PBS만을, 2군은 $^{131}I$-DC101 $50\;{\mu}g(200\;{\mu}Ci)$을, 3군은 DC101 $50\;{\mu}g$을, 4군은 $^{131}I$-DC101 $30\;{\mu}g(200\;{\mu}Ci)$을, 5군은 $^{131}I$-DC101 $15\;{\mu}g(200\;{\mu}Ci)$을 각각 매 3일 ${\sim}$ 4일마다 주사하고 전체 5회를 주사하였고 종양볼륨을 측정하였다. 결과: $^{131}I$-DC101을 흑색종 모델에 정맥주사하고 78시간까지 영상을 얻은 결과 시간에 따라 종양섭취가 증가 하는 영상을 보였다. 시간대별 장기섭취를 정확히 확인하기 위하여 1시간, 6시간, 24시간, 48시간, 72시간 장기섭취율을 비교한 결과 시간에 따라 혈액내 방사능치가 서서히 감소하였고 다른 장기의 섭취도 시간에 따라 감소하였고 종양의 섭취는 48시간까지 증가하였다가 그 이후는 감소하였다. 흑색종 동물모델에 $^{131}I$-DC101 치료를 시행한 결과 3번째 주사까지는 각군간의 유의한 차이를 보이지 않다가 4번째 주사를 시행한 때부터 1군과 2군, 또는 1군과 4군간의 유의한 차이를 보이기 시작했다. 또한 5번째 주사 이후에는 5군에서도 유의한 차이를 보여 I-131 에 의한 효과가 뚜렷해짐을 확인하였다. 결론 마우스 Flk-1 항체로 알려진 DC101을 흑색종 모델에 정맥내 주사하였을 때, 종양성장억제 효과를 보이지 않는 항체양에서도 I-131을 표지하여 치료를 시행했을 경우에는 효율적인 종양성장억제 효과를 보였다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6813-6823
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• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• Tuberculosis and Respiratory Diseases
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• 제66권3호
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• pp.178-185
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• 2009

연구배경: 암세포는 빠른 증식 속도로 인하여 상대적인 저산소증에 노출되면서 비정상적인 종양 혈관을 형성하여 치명적인 병인을 형성한다. EGCG는 녹차의 추출물로 간세포암주 및 전립선암주에서 HIF-1$\alpha$의 발현을 억제하는 것으로 알려져 있다. 그러나 EGCG의 비혈관 증식성 효과에 대해서는 아직 정확히 규명되어 있지 않다. 본 연구에서는 EGCG가 비소세포폐암주에서 HIF-1$\alpha$ 및 VEGF의 발현에 대한 억제 가능성을 확인하여 보고자 하였다. 방 법: 비소세포폐암주인 A549를 RPMI배지에서 계대 배양하였다. 저산소 유사 상태는 Modular Incubator Chamber (MIC-101)을 이용하였고 5% 이산화탄소와 95% 질소 혼합 가스를 5분 동안 공급하여 저산소 상태를 만들었으며 세포 배양액을 채취하여 혈액가스분석기(Blood Gas Analyzer ABL725)로 세포 배양 상태를 측정하였다. 세포의 증식 상태는 MTT 방법을 실시하였다. EGCG는 0, 12.5, 25, 50,100 ${\mu}mol/L$로 농도 변화를 주어 실험을 시행하였으며 16시간 동안 저산소 상태를 만든 뒤 HIF-1$\alpha$, VEGF, $\beta$-actin mRNA에 대해 Real time PCR을 시행하였다. 결 과: 48시간과 72시간에서 저산소 상태에 놓인 A549 세포의 증식능력은 대조군에 비하여 억제되었다. EGCG 는 저산소화에 의해 유도된 HIF-1$\alpha$의 mRNA의 전사를 유의하게 억제하였다. 그러나 이러한 억제 효과는 VRGF mRNA 발현에는 미치지 못하였다. 결 론: EGCG는 HIF-1$\alpha$의 발현을 억제함으로써 비소세포암주에서의 예방적 항암요법이나 항암 치료요법 시의 주요 작용 목표로 사용될 수 있을 것으로 보인다.