• Title/Summary/Keyword: VEGF-D

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Inhibition of Lymphatic Endothelial Growth Factor Receptor in a Murine Model of Oral Squamous Cell Carcinoma (구강 편평상피세포암 마우스 모델에서 림프관내피 성장인자 수용체의 억제)

  • Kye, Jun-Young;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.33 no.1
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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.

Effects of Hominis Placenta on the Growth of Human Uterine Myoma Cells and Cell Apoptosis (자하거(紫河車)가 자궁근종세포(子宮筋腫細胞)의 성장억제(成長抑制)와 세포자멸사(細胞自滅死)에 미치는 영향(影響))

  • Wee, Hyo-Sun;Lee, Jin-Moo;Lee, Chang-Hoon;Cho, Jung-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.2
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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 $10mg/m{\ell}$.

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Effects of Cervi Pontotrichum Cornu on Human Uterine Leiomyoma Cell in vitro (녹용(鹿茸)이 in vitro에서 자궁근종세포(子宮筋腫細胞)에 미치는 영향)

  • Lee, Yoon-Jae;Cho, Jung-Hoon;Lee, Chang-Hoon;Lee, Jin-Moo;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.2
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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.

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LncRNA LINC01232 Enhances Proliferation, Angiogenesis, Migration and Invasion of Colon Adenocarcinoma Cells by Downregulating miR-181a-5p

  • Yu Yuan;Zhou Long
    • Journal of Microbiology and Biotechnology
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    • v.33 no.3
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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.

Exploratory Analysis of Patients With Gastric/Gastroesophageal Junction Adenocarcinoma With or Without Liver Metastasis From the Phase 3 RAINBOW Study

  • Takatsugu Ogata;Yukiya Narita;Zev A. Wainberg;Eric Van Cutsem;Kensei Yamaguchi;Yongzhe Piao;Yumin Zhao;Patrick M. Peterson;Sameera R. Wijayawardana;Paolo Abada;Anindya Chatterjee;Kei Muro
    • Journal of Gastric Cancer
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    • v.23 no.2
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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.

Novel Heptapeptide Binds to the Lgr5 Induces Activation of Human Hair Follicle Cells and Differentiation of Human Hair Follicle Bulge Stem Cells (Lgr5와 결합하는 신규 헵타펩타이드를 이용한 인체 모낭 세포의 활성과 모낭줄기세포 분화 유도)

  • Min Woong Kim;Eung Ji Lee;Ha-Na Gil;Yong Ji Chung;Eun Mi Kim
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.49 no.1
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    • pp.75-85
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    • 2023
  • This study was conducted to assess the effect of heptapeptide, composed of seven amino acids, on the activation of human hair cells isolated from human hair follicles. We have confirmed that the heptapeptide could bind to Lgr5 from the results of surface plasmon resonance (SPR) analysis. Heptapeptide enhanced the proliferation of human hair follicle dermal papilla cells (HHFDPCs) in a dose dependent manner. It induced the protein level of nuclear β-catenin, and the expressions of β-catenin downstream target genes, including LEF1, Cyc-D1 and c-Myc, in HHFDPCs. Heptapeptide significantly induced the phosphorylation of Akt and ERK, and the mRNA expressions of growth factors, including hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF), in HHFDPCs. In addition, heptapeptide significantly increased mRNA expression levels of differentiation-related transcription factors of human hair germinal matrix cells (HHGMCs) and differentiation markers of human hair outer root sheath cells (HHORSCs). Additionally, we investigated the effect of heptapeptide on human hair follicle stem cells (HHFSCs) differentiation and found that the heptapeptide reduced the mRNA and protein levels of stem cell markers, while it increased those levels of differentiation markers. These results have indicated that the heptapeptide promotes proliferation or differentiation of various types of hair follicle constituent cells through the induction of Wnt/β-catenin signaling. From the results, we have suggested that the heptapeptide in this study could be applied as a new functional material for the improvement of hair growth and alopecia.

Fermented Ginseng with Bifidobacterium Inhibits Angiogenesis of Human Umbilical Endothelial Cells in vitro and in vivo

  • Ko, Yu-Jin;Park, Seung-Hee;Park, Byung-Chul;Lee, Yong-Hwa;Kim, Jung-Ae
    • Biomolecules & Therapeutics
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    • v.15 no.2
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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.

Hair Revitalization Effects of Streptococcus sp. Strain Culture Medium Filtrate (HAIRCLETM) (Streptococcus sp. 배양 여과물(HAIRCLETM)의 모발 개선 효과)

  • Park, Hye Rim;Kim, Ha Yeon;Kim, Jin Young;Oh, Sinseok;Kang, Pilsun;Lee, Gang Hyuk;Lim, Jung-Hyurk;Shin, Song Seok
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.48 no.2
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    • pp.169-180
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    • 2022
  • Streptococcus sp. is generally known as a strain that produces hyaluronic acid. In this study, we focused on ingredients other than hyaluronic acid among several metabolites produced by Streptococcus sp. during cultivation. The hair experimental sample (HAIRCLETM) was prepared with Streptococcus sp. culture filtrate under the condition that hyaluronic acid was not produced and the effect on the hair was identified. Tensile strength of hair was tested with a universal testing machine (UTM). Surface properties of a hair were examined with an atomic force microscope (AFM). Our results suggest that HAIRCLETM could prevent damage to a hair such as destroyed-cuticle, increased-faction force, and broken-hair. Furthermore, hair-related experiments confirmed that HAIRCLETM could promote the expression of hair growth factors VEGF, HGF, and Wnt10b and mitigate male hair loss by inhibiting androgen receptors and TGF-β2 expression. In addition, it was confirmed that the expression of barrier-related factors (INV, CLDN-1) was increased for oxidative stress, and the COX-2 expression, an inflammatory factor, was inhibited, thereby improving damaged scalp barriers and alleviating induced inflammation.

RK-270D and E, Oxindole Derivatives from Streptomyces sp. with Anti-Angiogenic Activity

  • Jang, Jun-Pil;Jang, Mina;Nogawa, Toshihiko;Takahashi, Shunji;Osada, Hiroyuki;Ahn, Jong Seog;Ko, Sung-Kyun;Jang, Jae-Hyuk
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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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.