• Title/Summary/Keyword: Inhibition Factor

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CONCOMITANT INHIBITION OF EPIDERMAL GROWTH FACTOR AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR TYROSINE KINASES IN ORAL SQUAMOUS CELL CARCINOMA (구강 편평상피세포암에서 상피성장인자 수용체와 혈관내피성장인자 수용체 타이로신 활성화효소의 동시 억제)

  • Park, Young-Wook;Lee, Sang-Shin
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.3
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    • pp.193-201
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    • 2006
  • Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

Isolation of Bacillus amyloliquefaciens H41 Producing Growth Inhibition Factor against Vibrio anguillarum (어병균 Vibrio anguillarum 생육 저해 인자를 생산하는 Bacillus amyloliquefaciens H41의 분리)

  • Kim, Young-Hee;Jeong, Yong-Kee;Chung, Kyung-Tae;Rhu, Eun-Ju;Jeong, Yu-Jeong
    • Journal of Life Science
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    • v.16 no.4
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    • pp.605-611
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    • 2006
  • To investigate the possible use of probiont in fish farming industry, a bacterium with inhibitory effect against Vibrio anguillarum was isolated from gastrointestinal tract of the marine fish of yellow tail. It was identified to be Bacillus amyloliquefaciens H41 based on biochemical and physiological characterization. The optimal growth conditions of the isolated strain were 1% peptone, 1.5% yeast extract, 1% sucrose, 0.5% NaCl, 0.05% $MgSO_4{\cdot}7H_20$, pH 7.0-8.0, and 20 hr of incubation between $28-35^{\circ}C$ under aeration. The culture supernatant of the isolated strain showed inhibition activity against V. anguillarum. Inhibition activity was cleared by forming a clear zone by a paper-disk method. The maximal production of growth inhibition factor was induced by cultivation under 1% peptone, 1.5% yeast extract, 1% sucrose, 1% NaCl, 0.05% $MgSO_4{\cdot}7H_20$, pH 7.5 and at $35^{\circ}C$. The highest growth inhibition factor production was observed after 16-24 hr cultivation under aeration. The culture supernatant of the isolated strain showed inhibition activity whereas no inhibition activity was shown from the standard B. amyloliquefaciens KCTC 1724 strain. The growth inhibition affected only against V. anguillarum among other pathogenic Vibrios tested here.

Purification of Vibrio anguillarum Growth Inhibition Factor Produced by Bacillus amyloliquefaciens H41. (Bacillus amyloliquefaciens H41이 생산하는 Vibrio anguillarum 생육 저해인자의 정제)

  • Shin, Hyun-Chul;Chung, Kyung-Tae;Kim, Kwang-Hyun;Kim, Byung-Woo;Kwon, Hyun-Ju;Lee, Eun-Woo;Yum, Jong-Hwa;Rhu, Eun-Ju;Jeong, Yu-Jeong;Kim, Young-Hee
    • Journal of Life Science
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    • v.18 no.6
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    • pp.789-795
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    • 2008
  • To study the possible use of probiotics in fish farming, we evaluated antagonism of antibacterial strain Bacillus amyloliquefaciens H41 against the fish pathogenic bacterium Vibrio anguillarum NCMB1. The purification of growth inhibition factor produced by B. amyloliquefaciens H41 was achieved by obtaining supernatant of this bacterium. The growth inhibition factor was purified to homogeneity by 70% ammonium sulfate precipitation, DEAE-sephadex A-50 ion exchange chromatography, sephadex G-200 gel filtration column chromatography, and sephadex G-50 gel filtration column chromatography with 40.8 fold of purification and 2.9% yield. The molecular weight of the purified growth inhibition factor was 48 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The optimum pH and temperature for the growth inhibition factor were pH 7.5 and $30^{\circ}C$, respectively. The activity of growth inhibition factor was enhanced slightly by some metal ions, such as $Mg^{+2}$, $Mn^{+2}$, but was inhibited by the addition of $Co^{+2}$, $Hg^{+2}$, $Zn^{+2}$ and $Ag^{+2}$. NaCl stability of the growth inhibition factor was observed with 50% residual activity at 3% NaCl concentration. Toxicity test showed that the purified B. amyloliquefaciens H41 growth inhibition factor did not affect the live of Japanese flounder (Paralichthys olivaceus) and the effectiveness was 78% of residual lethality compared to commercial antibacterial agents.

Inhibition of Hepatocellular Carcinoma Cell Growth by the Extract of Symphytum offcinale L. and the Possible Mechanisms for this Inhibition

  • Ham, Seung-Shi;Park, Kyong-Gun;Lee, Yong-Moon;Lee, Young-Ik;Yoon, Ji-Won;Kim, Seong-Jin;Lee, euk-Sik
    • Preventive Nutrition and Food Science
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    • v.2 no.3
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    • pp.236-240
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    • 1997
  • A crude extract of Smphytum officinale L. (comfrey) was for its ability to inhibit he growth of hepatocellular carcinoma cells and expression of the insulin-like growth factor I (IGF-II) gene. The DNA synthesis of hepatocellular carcinoma cell lines, Hep G2, Hep 3B, and PLC/PRF/5 was inhibited by a crude extract of Smphytum officinale in both a time- and a dose-dependent manners. This plant extract also inhibited expression of the IGF-II gene. Since IGF-II exerts a mitogenic effect on Hep G2 cells, these results suggest that the growth inhibition by Symphytum officinale extract is, in part, mediated through the inhibition of IGF-II gene expression.

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Growth inhibition in head and neck cancer cell lines by gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (두경부암 세포주에서 상피성장인자수용체 타이로신 카이네이즈 억제제인 gefitinib의 성장억제에 관한 연구)

  • Song, Seung-Il;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.35 no.5
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    • pp.287-293
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    • 2009
  • Cell survival is the result of a balance between programmed cell death and cellular proliferation. Cell membrane receptors and their associated signal transducing proteins control these processes. Of the numerous receptors and signaling proteins, epidermal growth factor receptor (EGFR) is one of the most important receptors involved in signaling pathways implicated in the proliferation and survival of cancer cells. EGFR is often highly expressed in human tumors including oral squamous cell carcinomas, and there is increasing evidence that high expression of EGFR is correlated with poor clinical outcome of common human cancers. Therefore, we examined the antiproliferative activity of gefitinib, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), in head and neck cancer cell lines. SCC-9, KB cells were cultured and growth inhibition activity of gefitinib was measured with MTT assay. To study influence of gefitinib in cell cycle, we performed cell cycle analysis with flow cytometry. Western blot was done to elucidate the expression of EGFR in cell lines and phosphorylation of EGFR and downstream kinase protein, Erk and Akt. Significant growth inhibition was observed in SCC-9 cells in contrast with KB cells. Also, flow cytometric analysis showed G1 phase arrest only in SCC-9 cells. In Western blot analysis for investigation of EGFR expression and downstream molecule phosphorylation, gefitinib suppressed phosphorylation of EGFR and downstream protein kinase Erk, Akt in SCC-9. However, in EGFR positive KB cells, weak expression of active form of Erk and Akt and no inhibitory activity of phosphorylation in Erk and Akt was observed. The antiproliferative activity of gefitinib was not correlated with EGFR expression and some possibility of phosphorylation of Erk and Akt as a predictive factor of gefitinib response was emerged. Further investigations on more reliable predictive factor indicating gefitinib response are awaited to be useful gefitinib treatment in head and neck cancer patients.

Relationships between Adolescent's Behavioral Inhibition and Social Anxiety : Moderating Effects of Perceived Parental Rearing Behaviors (청소년의 행동억제기질과 사회불안의 관계에서 지각된 부모양육행동의 중재효과)

  • Kim, Ji-Won;Ha, Eun-Hye;Cho, You-Jin
    • Korean Journal of Child Studies
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    • v.30 no.6
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    • pp.535-548
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    • 2009
  • The purpose of this study was to investigate relationships between adolescent's behavioral inhibition and social anxiety focused on the moderating effects of perceived parental rearing behaviors. Subjects were 749 7th through 9th grade students attending schools in Seoul and Gyeonggi Province. Major findings were that (1) boys' and girls' behavioral inhibition was an important factor predicting social anxiety; and (2) perceived parental rearing behaviors played the role of moderating variables on the influence of behavioral inhibition of boys' and girls' social anxiety. In the boys' group, perceived intrusion had a moderating effect on the relationships between behavioral inhibition and social anxiety; in the girls' group, perceived warmth and perceived granting of autonomy acted as moderating variables on social anxiety.

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Studies on the Antiinflammatory Effects of Natural Products (천연물의 항염증작용에 관한 연구)

  • 유태무;이숙영;정수연;승상애;류항묵;양지선;이은방
    • Biomolecules & Therapeutics
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    • v.6 no.3
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    • pp.269-275
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    • 1998
  • These studies were conducted to investigate the antiinflammatory effects and the mechanism of action of natural products. We used the methods of "carrageenan induced foot edema" , "PAF (platelet activating factor) induced foot edema" , "inhibition test of vascular permeability" , "inhibition test of white blood cell migration" , "formation of granuloma" and "adjuvant induced arthritis" to examine the antiinflammatory erects of Angelica gigas, Ledebouriella seseloides, Ginkgo biloba and Bamboo salt (Jukyom). The oral administration of the water extract of Angelica gigantis radix, the methanolic extract of Ginkgo folium and the aqueous solution of Bamboo salt showed antiinflammatory effect on carrageenan and PAF induced foot edema in SD rat at a dose of 1 g/kg. The same administration of methanolic extract of Ginkgo folium also inhibited the vascular permeability in mice. The aqueous solution of Bamboo salt inhibited the formation of ganuloma in SD rats at a oral dose of 1 g/kg. Angelica gigantis radix seems to have antiinflammatory effect by inhibition of PAF.

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Structure-Activity Relationships of Fungicidal N-Substituted Phenyl 1,3,5- Trimethylpyrazole-4-carboxamides in the Inhibition of Succinate Dehydrogenase (SDH) Isolated from Rhizoctonia solani $K{\ddot{u}}hn$ (벼 잎집무늬 마름병균 (Rhizoctonia solani $K{\ddot{u}}hn$)에서 분리한 Succinate Dehydrogenase (SDH) 에 대한 N-치환 phenyl 1,3,5-trimethylpyrazole-4-carboxamide 유도체의 효소활성저해)

  • Kim, Yong-Whan
    • Applied Biological Chemistry
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    • v.40 no.5
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    • pp.447-450
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    • 1997
  • Eighteen N-substituted phenyl 1, 3, 5-trimethylpyrazole-4-carboxamides were synthesized to screen for their mycelial growth inhibition activity against Rhizoctonia solani $K{\ddot{u}}hn$ $(pEC_{50})$ and to measure enzymatic inhibition activity of these compounds $(pI_{50})$ against succinate dehydrogenase (SDH) isolated from Rhizoctonia solani $K{\ddot{u}}hn$ A structure-activity relationship formulated by regression analysis showed that 79% of the variance in mycelial growth inhibition activity can be explained with SDH inhibition activity and chromatographic capacity factor $(\acute{k})$ as a hydrophobic parameter related to the penetration and transport processes in the biological system.

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Effects of Tumor Necrosis Factor Alpha on Growth and Tube Formation of Bovine Vascular Endothelial Cells in vitro

  • Yoon, Duc-;Hwa-Joong
    • Toxicological Research
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    • v.11 no.2
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    • pp.169-173
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    • 1995
  • The effects of tumor necrosis factor alpha $(TNF-{\alpha})$ on growth and tubular formation of bovine aortic endothelial cells were examined using an in vitro angiogenesis model system. The growth of endothelial cells was enhanced in a dose-dependent manner when the cells were cultured with $TNF-{\alpha}$ for 3 days, but $TNF-{\alpha}$, at the concentration of 1 nM or higher, produced a growth inhibition of endothelial cells when the cells were cultured for 8 days. The endothelial cells incubated with $TNF-{\alpha}$ for 48-h exhibited a typical morphologic change. Then, they showed a fibroblastoid organization of overlapping, elongated, and spindle-shaped cells. $TNF-{\alpha}$, at the concentration of O. 1 nM or higher, inhibited the tubular formation of vascular endothelial cells in an in vitro anglogenesis model using a 3-dimensional culture system.

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