• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권1호
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• pp.1-9
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• 2011

Purpose: Tumor associated angiogenesis and/or lymphangiogenesis are known to be linked by VEGFR signaling pathways. These processes are regulated by several growth factors including VEGFR-2, VEGFR-3. E7080 is an orally active inhibitor of multiple tyrosine kinases including VEGFR-2, 3. Therefore, it was proposed that E7080 may inhibit angiogenesis and lymphangiogenesis. The aim of this study was to determine the effect of E7080 in a nude mouse model of OSCC. Methods: KB cells were xenografted into the submucosal tissue of the mouth floor of athymic mice. Seven days after the xenograft, the mice were randomized into 2 groups. E7080 were administered orally to the experimental group once per day. The mice were sacrificed 3 weeks after the treatment. The tumors were examined histopathologically. Immunohistochemical assays with anti- VEGF-C, VEGFR-2, VEGFR-3, phosphorylated VEGFR-2/3 (pVEGFR-2/3), and D2-40 antibodies were then performed. Results: The transplantation of human OSCC tumor cells into the mouth floor resulted in the formation of orthotopic tumors. The experimental (E7080 treatment) group showed a slowly increased tumor volume. Moreover, immunohistochemical staining demonstrated higher levels of VEGF-C, VEGFR-2, VEGFR-3, pVEGFR-2/3 and D2-40 expression in the control group than in the experimental group. Conclusion: These results suggest that E7080 may provide therapeutic benefits in OSCC.

• 대한한방부인과학회지
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• 제21권2호
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• pp.38-48
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• 2008

Purpose: This study was conducted to investigate the effects of Hominis Placenta (紫河車) on the growth of human uterine myoma cells and cell apoptosis. Methods: Human uterine leiomyoma cells were cultured and treated with Hominis Placenta extract for 48 hours. Cell proliferation and activity was analyzed by MTT assay. We analyzed the cell cycle of human uterine myoma cells treated Hominis Placenta extract by FACS. Expression of proteins related to cell apoptosis (Bax, Bcl-2), cyclin-D1 and VEGF were evaluated by Western blotting method. Results: The human uterine myoma cells treated by Hominis Placenta extract didn't proliferate below the concentration of $10mg/m{\ell}$. And there was no remarkable difference on cell cycle analysis below the concentration of $10mg/m{\ell}$. The expression of Bax was decreased and the expression of Bcl-2 was increased after the treatment of Hominis Placenta extract. But the expressions of cyclin-D1 and VEGF were increased after the treatment of Hominis Placenta extract. Conclusion: This study suggests that Hominis Placenta induce uterine myoma cell apoptosis and have effect on the myoma cell proliferation in the concentraion below $10mg/m{\ell}$.

• 대한한방부인과학회지
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• 제21권2호
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• pp.17-26
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• 2008

Purpose: This study was conducted to investigate the effects of Cervi Pontotrichum Cornu extract solution on the cell cycle regulation and apoptosis in human leiomyoma cell. Methods: The leiomyoma cell of patients was used in the study, and we administered the extract solution of Cervi Pontotrichum Cornu concentration at 1, $10mg/m{\ell}$ to the leiomyoma cell for 48 hours. We used flow cytometry and western blotting to confirm cell cycle and apoptosis. Results: In flow cytometry, G1 phase of the $1mg/m{\ell}$ group prolonged. But G1 phase of $10mg/m{\ell}$ group was shortened and S phase was increased. Cyclin D1 expression increased in higher concentration group. And Bax expression that regulates cell apoptosis increased in $1mg/m{\ell}$ and $10mg/m{\ell}$ group than control group. Bcl-2 expression decreased in 1, $10mg/m{\ell}$ groups than control group. VEGF expression rised in higher Cervi Pontotrichum Cornu concentration group. Conclusion: This study means that Cervi Pontotrichum Cornu could induce the apoptosis of leiomyoma cell by increasing Bax and decreasing Bcl-2 expression. But Cervi Pontotrichum Cornu could increase Cyclin D1 and VEGF expression, so more detailed studies would be needed.

• Journal of Microbiology and Biotechnology
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• 제33권3호
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• pp.398-409
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• 2023

LncRNAs play crucial roles in the progression of colon adenocarcinoma (COAD), but the role of LINC01232 in COAD has not received much attention. The present study was designed to explore the related mechanisms of LINC01232 in the progression of COAD. LINC01232, miR-181a-5p, p53, c-myc, Bcl-2, cyclin D1, p16, Bax, VEGF, E-cadherin, vimentin, N-cadherin and SDAD1 expressions were determined by western blot and qRT-PCR. CCK-8, tubule formation, and Transwell assays were employed to detect proliferation, angiogenesis, and migration/invasion of COAD cells, respectively. The relationship between LINC01232 and miR-181a-5p was predicted by LncBase Predicted v.2, and then verified through dual luciferase reporter gene assay. According to the results, LINC01232 was highly expressed in COAD cells and enhanced proliferation, angiogenesis, migration, and invasion of COAD cells. Downregulated LINC01232 promoted expression of p53 and p16, and inhibited c-myc, Bcl-2 and cyclin D1 expressions in COAD cells, while upregulation of LINC01232 generated the opposite effects. LINC01232 was negatively correlated with miR-181a-5p while downregulated miR181a-5p could reverse the effects of siLINC01232 on cell proliferation, angiogenesis, migration, and invasion. Similarly, miR-181a-5p mimic could also offset the effect of LINC01232 overexpression. SiLINC01232 increased the expressions of Bax and E-cadherin, and decreased the expressions of VEGF, vimentin, N-cadherin and SDAD1, which were partially attenuated by miR-181a-5p inhibitor. Collectively, LINC01232 enhances the proliferation, migration, invasion, and angiogenesis of COAD cells by decreasing miR-181a-5p expression.

• Journal of Gastric Cancer
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• 제23권2호
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• pp.289-302
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• 2023

Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.

• 대한화장품학회지
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• 제49권1호
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• pp.75-85
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• 2023

본 연구에서는 7 개의 아미노산으로 이루어진 헵타펩타이드의 Lgr5 binding에 따른 인체 모낭 구성 세포의 활성에 대한 영향을 확인하였다. 표면 플라즈몬 공명(surface plasmon resonance, SPR) 시스템을 이용하여 헵타펩타이드가 Lgr5에 결합하는 것을 확인하였다. 인체 모유두세포(human hair follicle dermal papilla cell, HHFDPC)에 헵타펩타이드를 처리한 결과, 농도 의존적인 세포 증식이 나타났으며 β-catenin의 세포 내핵 이동 및 하위 유전자인 LEF1, Cyclin-D1, c-Myc의 발현 증가가 관찰되었다. 그리고 세포 증식 기전 관련 인자인 Akt와 ERK의 인산화 수준이 증가되었으며, 성장인자인 hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF) 발현이 유도되었다. 또한 인체 모모세포(human hair germinal matrix cell, HHGMC)의 분화 관련 전사 인자와 인체 외모근초세포(human hair outer root sheath cell, HHORSC)의 분화 표지 인자들도 헵타펩타이드 처리 시 높은 발현율을 보였다. 추가적으로 우리는 헵타펩타이드의 인체 모낭줄기세포(human hair follicle stem cell, HHFSC) 분화에 대한 영향을 조사하였다. 그 결과, HHFSC 표지인자들의 mRNA와 단백질 수준이 감소하였고 반면에 분화 표지인자들은 증가하였다. 상기의 결과들은 헵타펩타이드가 인체 모낭 구성 세포에서 Wnt/β-catenin 경로를 촉진시켜 증식 또는 분화를 유도할 수 있음을 보여준다. 이를 토대로 종합해 볼 때, 본 연구의 헵타펩타이드는 모발 성장을 유도하고 탈모 개선에 도움을 줄 수 있는 기능성 원료로 사용될 수 있을 것으로 보인다.

• Biomolecules & Therapeutics
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• 제15권2호
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• pp.89-94
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• 2007

Ginseng is a widely-used alternative medicine for the treatment of cancer, diabetes, and cardiovascular diseases. Active components of P. ginseng, absorbed through gastrointestinal tract are the fermented ginsenosides by intestinal microorganisms. In the present study, we investigated the inhibitory effects of fermented ginseng with bifidobacterium (FGb) on the angiogenesis by analyzing in vitro tube formation and invasion assay using human umbilical vein endothelial cells (HUVECs), and in vivo angiogenesis using chick chorioallantoic membrane (CAM) assay. Treatment with FGb inhibited tube-like structure formation in a concentration-dependent manner. In addition, FGb significantly suppressed HUVEC invasion through Matrigel. Moreover, FGb dosedependently inhibited VEGF-induced angiogenesis in a CAM assay. These results suggest that FGb is a valuable anti-angiogenic remedy.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2005년도 제48차 춘계 학술대회
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• pp.128-128
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• 2005

• 대한화장품학회지
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• 제48권2호
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• pp.169-180
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• 2022

Streptococcus sp.는 일반적으로 히알루론산을 생산하는 균주로 알려져 있다. 본 연구에서는 Streptococcus 균주가 배양하면서 만들어내는 여러 대사산물 중 히알루론산 이외의 영양성분에 주목하였다. 히알루론산이 생성되지 않은 조건에서의 Streptococcus sp. 배양 여과물로 모발 실험용 샘플(HAIRCLE^TM)을 제조하고 모발에 미치는 효과를 확인하였다. 모발의 인장강도는 만능시험기(universal testing machine, UTM)로 측정하였으며, 모발표면의 미세구조는 atomic force microscope (AFM)으로 분석하였다. 이 연구를 통해 Streptococcus sp. 배양 여과물은 손상된 모표피개선, 마찰력증가 및 모발강도의 증가 등의 모발개선 효과가 있는 것으로 확인되었다. 또한 in vitro 모발관련 실험을 통해 Streptococcus sp. 배양 여과물이 모발성장인자인 혈관내피세포 성장인자(vascular endothelial growth factor, VEGF), 간세포성장인자(hepatocyte growth factor, HGF), Wnt10b의 발현 촉진 효과가 있음을 확인 하였으며, 안드로젠 수용체(androgen receptor, AR)와 TGF-β2 발현을 저해시켜 남성형 탈모완화 효과도 있음을 확인 하였다. 또한 산화스트레스에 대해 장벽 관련 인자(INV, CLDN-1)의 발현을 증가시키고, 염증성 인자인 COX-2 발현을 억제시킴으로써 손상된 두피 장벽을 개선하고 유도된 염증을 완화시키는 효능이 있음을 확인하였다.

• Journal of Microbiology and Biotechnology
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• 제32권3호
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• pp.302-306
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• 2022

A chemical investigation of a culture extract from Streptomyces sp. RK85-270 led to the isolation and characterization of two new oxindoles, RK-270D (1) and E (2). The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and High-resolution electrospray ionization mass spectrometry (HRESIMS) experiments. Compound 1 exhibited anti-angiogenic activities against human umbilical vein endothelial cells (HUVECs) without cytotoxicity. Results of Western blot analysis revealed that 1 inhibits VEGF-induced angiogenesis in the HUVECs via VEGFR2/ p38 MAPK-mediated pathway.