• Title/Summary/Keyword: MCL1

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YM155 Induces Apoptosis through Downregulation of Anti-apoptotic Proteins in Head and Neck AMC-HN4 Cells (YM155 처리에 의한 두경부 암 AMC-HN4 세포 세포자멸사 유도 효과)

  • Chang, Ho Joon;Kwon, Taeg Kyu;Kim, Dong Eun
    • Journal of Life Science
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    • v.29 no.3
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    • pp.318-324
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    • 2019
  • Squamous cell carcinoma is the primary tumor type in head and neck cancers, the fifth most common malignant neoplasm world-wide. Survivin, a member of the inhibitor of apoptosis family, is highly expressed in head and neck carcinoma patients and correlated with more aggressive forms. In this study, we investigated whether YM155, a specific survivin inhibitor, could induce apoptosis in head and neck AMC-HN4 cells. YM155 was found to markedly induce apoptosis and cleavage of PARP, a marker of apoptosis. Furthermore, YM155 promoted apoptosis in other cancer cells, such as glioma (U251MG) and renal carcinoma (Caki) cells. In contrast, YM155 had no effect on apoptosis in normal mesangial cells. YM155 significantly induced caspase activation, and pan caspase inhibitor z-VAD-fmk markedly blocked apoptosis, PARP cleavage, and caspase-3 cleavage. Therefore, YM155 was seen to instigate caspase-dependent apoptosis in head and neck AMC-HN4 cells, inducing downregulation of survivin as well as other apoptotic proteins such as c-FLIP and Mcl-1. In addition, the induction of apoptosis and PARP cleavage by YM155 treatment was effectively inhibited in survivin-, c-FLIP- and Mcl-1-over-expressing head and neck AMC-HN4 cells. In conclusion, YM155 is a potent candidate for inducing cell death in head and neck AMC-HN4 cells.

Audiological Findings of Congenital Ichthyosiform Dermatosis with Sensorineural Hearing Loss (난청을 동반한 선천성 어린선상 피부병의 청각학적 소견)

  • 한태희;최진택;김광현;박찬일
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1981.05a
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    • pp.40.3-41
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    • 1981
  • The ichthyosiform dermatosis is consisted of a heterogenous group of hereditary disorders. Authors report a case of 26 year old female patient who has congenital ichthyosiform dermatosis associated with sensorineural hearing loss, neovascularization of cornea, partial alopecia and abnormalities of nails and teeth. The audiological findings of this patient were as follows: 1. Bilateral severe sensorineural hearing loss. 2. SISI scores: 100% at 1, 000 Hz and 4, 000 Hz on both ear. 3. Tone decay test: 25 dB decay at 1, 000 Hz and 4, 000 Hz respectively on both ear. 4. SRTs : 85 dB on both ear. 5. Speech discrimination scores : 80% at 95 dB hearing level(MCL) on both ear. With above results, cochlear lesion is suspected in this syndrome.

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Purification and Cloning of an Extracellular Serine Protease from the Nematode-Trapping Fungus Monacrosporium cystosporium

  • Yang, Jin-Kui;Ye, Feng-Ping;Mi, Qi-Li;Tang, Song-Qing;Li, Juan;Zhang, Ke-Qin
    • Journal of Microbiology and Biotechnology
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    • v.18 no.5
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    • pp.852-858
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    • 2008
  • An extracellular protease (Mc1) was isolated from the nematode-trapping fungus Monacrosporium cystosporium by gel filtration, anion-exchange, and hydrophobic interaction chromatographies. This protease had a molecular mass of approximately 38 kDa and displayed an optimal activity at pH 7-9 and $56^{\circ}C$ (over 30 min). Its proteolytic activity was highly sensitive to the serine protease inhibitor PMSF (phenylmethylsulfonylfluoride, 0.1 mM), indicating that it belonged to the serine-type peptidase group. The Michaelis constant ($K_m$) and $V_max$ for substrate N-Suc-Ala-Ala-Pro-Phe-pNA were $1.67{\times}10^{-4}\;M$ and 0.6071 $OD_{410}$ per 30 s, respectively. This protease could degrade a broad range of substrates including casein, gelatin, BSA (bovine serum albumin), and nematode cuticle. Moreover, the enzyme could immobilize the free-living nematode Panagrellus redivivus and the pine wood nematode Bursaphelenchus xylophilus, suggesting that it might playa role in infection against nematodes. The encoding gene of Mc1 was composed of one intron and two exons, coding for a polypeptide of 405 amino acid residues. The deduced amino acid sequence of Mcl showed 61.4-91.9% identity to serine proteases from other nematode-trapping fungi. Our results identified that Mcl possessed biochemical properties including optimal reaction condition and substrate preference that are different from previously identified serine proteases.

Quality Characteristics and Evaluation of Physiological Activities of Moju Made with Hovenia dulcis Thunb. (헛개나무를 이용한 모주의 품질 특성 및 생리활성(in vivo) 효능 검증)

  • Park, Yeon-Hee;Yu, Ok-Kyeong;Bae, Cho-Rong;Cha, Youn-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.11
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    • pp.1599-1606
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    • 2015
  • The purpose of this study was to assess the quality characteristics of Moju made with Hovenia dulcis Thunb. and its physiological effects on ICR mice. According to the sensory score, we selected Moju made with 1% Hovenia dulcis Thunb. among Moju made with 0, 0.5, 1, 5, and 10% Hovenia dulcis Thunb. Compared to Moju made without Hovenia dulcis Thunb., Moju made with 1% Hovenia dulcis Thunb. had higher proportions of moisture (86.77 g/100 g) and carbohydrates (11.86 g/100 g). The mean values of the physicochemical analyses were as follows: pH 4.91, acidity 0.28, $^{\circ}Brix$ 12.63, reducing sugar 68.97, alcohol content 0.1, alcohol density 0.998. Moju made with 1% Hovenia dulcis Thunb. did not have effects on DPPH radical scavenging activity; however, superoxide dismutase activity was significantly higher than that of Moju made without Hovenia dulcis Thunb. For assessing physiological activities, 4-week-old male ICR mice were divided into six groups (n=10): normal control group (NC), ethanol-administered group (EC), EC plus low-dose Moju made with 0% Hovenia dulcis Thunb. (MCL), EC plus high-dose Moju made with 0% Hovenia dulcis Thunb. (MCH), EC plus low-dose Moju made with 1% Hovenia dulcis Thunb. (MDL), and EC plus high-dose Moju made with 1% Hovenia dulcis Thunb. (MDH). Serum triglyceride (TG) level was reduced by 11.17% and 19.61% in the MDL and MDH groups, respectively, compared to the EC group. Serum total-cholesterol levels of MDL and MDH groups were significantly lower as compared to the EC group. Serum high-density lipoprotein-cholesterol levels of the MDL and MDH groups were significantly higher than those of the EC group. Liver TG levels were significantly reduced in the MCL and MDL groups. From these results, Moju made with Hovenia dulcis Thunb. demonstrated antioxidant activity and reduction of hyperlipidemia markers. Therefore, Moju made with Hovenia dulcis Thunb. can serve as a non-alcoholic beverage and functional food source.

Uranium and Radon Concentrations in Groundwater near the Icheon Granite (이천 화강암지역 지하수의 우라늄과 라돈 함량 특성)

  • Cho, Byong-Wook;Choo, Chang-Oh;Kim, Moon-Su;Lee, Young-Joon;Yun, Uk;Lee, Byeong-Dae
    • The Journal of Engineering Geology
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    • v.21 no.3
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    • pp.259-269
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    • 2011
  • Concentrations of uranium (U) and radon (Rn) were measured in groundwater from 74 wells in the Icheon area, with the aim of determining the range and distribution of concentrations in an area underlain by granite (in this case, the Icheon granite). U concentrations ranged from 0.02 to 1,640.0 ${\mu}g/L$ (median value, 2.03 ${\mu}g/L$) and Rn concentrations ranged from 40 to 23,400 pCi/L (median value, 4,649 pCi/L). U concentrations in 10.8% of the samples exceeded 30 ${\mu}g/L$, which is the maximum contaminant level (MCL) proposed by the US Environmental Protection agency (EPA), based on the chemical toxicity of U. In addition, U concentrations in 59.5% and 13.5% of the samples exceeded 4,000 pCi/L (the Alternative MCL (AMCL) of the US EPA) and 8,100 pCi/L (Finland’s guideline level), respectively. We found no significant correlations between U (Rn) and other constituents, except for U-$HCO_3$ (correlation coefficient of 0.71), U-Ca (0.69), U-Li (0.45), U-Sr (0.43), and U-F (0.42). U and Rn contents in the groundwater are low relative to those in areas in other countries with similar geological settings, possibly due to the inflow of shallow groundwater to the wells in the Icheon area.

Combined Treatment with Stattic and Docetaxel Alters the Bax/Bcl-2 Gene Expression Ratio in Human Prostate Cancer Cells

  • Mohammadian, Jamal;Sabzichi, Mehdi;Molavi, Ommoleila;Shanehbandi, Dariush;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.5031-5035
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    • 2016
  • Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the $2^{{\Delta}{\Delta}CT}$ method. The $IC_{50}$ values for docetaxel and stattic were $3.7{\pm}0.9nM$ and $4.6{\pm}0.8{\mu}M$, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.

RUNNING TITLE: APOPTOTIC EFFECT OF MYCOLACTONE IN SCC15 CELLS (구강편평세포암종 세포주 SCC15에서 Mycolactone에 의한 apoptosis 효과)

  • Kim, Jae-Woo;Song, Jae-Chul;Lee, Hee-Kyung;Lee, Tae-Yoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.6
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    • pp.511-518
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    • 2001
  • The effect of mycolactone, a recently reported apoptosis-inducing factor, was investigated in SCC15 oral squamous cell carcinoma(OSCC) cell line. Mycolactone rapidly induced cell death in OSCC cells in 2days, which was similar to that found in apoptotic cell such as detaching from culture plate and rounding-up of cells. Apoptotic cells were increased 4hrs after mycolactone treatment and more than half of cells showed apoptosis after 72hrs. Caspase 3 activation a biochemical evidence of apoptosis, was determined by Western blotting. Caspase 3 activation was started at 2hrs that lasted until 8hrs after mycolactone treatment. The expression of bcl-2 family genes was determined to explain the mechanism of apoptosis found in OSCC cells. The expressions of bad, bak, and bax (pro-apoptotic genes) and bcl-w and bcl-2 genes (anti-apoptotic genes) were not changed by mycolactone treatment. The expression of bcl-xi was decreased 8 hrs after mycolactone treatment. Mcl-1 expression was initially increased at 2 hrs which was decreased 8 hrs after mycolactone treatment. The down-regulation of these two anti-apoptotic genes might explain the mycolactone-induced apoptosis in OSCC cells. In this study, mycholactone was revealed to induce cell death in OSCC cells apoptosis and the apoptosis mechanism of OSCC cells was shown to be down-regulation of anti-apoptotic genes, bcl-xi and mcl-1. These results suggested the applicability of mycolactone for the development of an anti-cancer drug candidate by inducing apoptosis of OSCC cancer cell.

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Artemisia capillaris Thunb. inhibits cell growth and induces apoptosis in human hepatic stellate cell line LX2

  • Kim, Young-Il;Lee, Jang-Hoon;Park, Seung-Won;Choi, In-Hwa;Friedman, Scott L.;Woo, Hong-Jung;Kim, Young-Chul
    • Advances in Traditional Medicine
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    • v.10 no.4
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    • pp.254-262
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    • 2010
  • Artemisia capillaris (A. capillaries) is known to play roles in many cellular events, such as cell proliferation, differentiation, and apoptosis. We investigated the antifibrogenic efficacy of A. capillaris in the immortalized human hepatic stellate cell line LX2. Cell proliferation was determined by the MTT assay. Cell cycle was analyzed by the flow cytometry. Apoptotic cells were measured using a cell death detection ELISA. Caspase activity was detected by a colorimetric assay. The mRNA level of Bcl-2 and Bax mRNA were measured by real-time PCR. MEK and ERK protein were detected by Western blot analysis. We provide evidence that A. capillaris induces cell cycle arrest, apoptosis, and potently inhibits the mitogen-activated protein kinase pathway. A. capillaris inhibited cell proliferation of LX2 cells in a dose- and time-dependent manner, increased the apoptosis fraction at cell cycle analysis with an accompanying DNA fragmentation, and resulted in a significant decrease in Bcl-2 mRNA levels and an increase in Bax expression. Exposure of LX2 cells to A. capillaris induced caspase-3 activation, but co-treatment of A. capillaris with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. A. capillaris down-regulated Mcl-1 protein levels and inhibited phosphorylation of MEK/ERK, suggesting that it mediates cell death in LX2 cells through the down-regulation of Mcl-1 protein via a MEK/ERK-independent pathway.

Analysis of Interference Impact of UWB System on WiBro System (UWB 시스템에 의한 WiBro 시스템에서의 간섭영향에 관한 연구)

  • Yoon Young-Keun;Hong Heon-Jin;Lee Il-Kyoo;Choi Ik-Guen;Kwak Kyung-Sub
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.31 no.8A
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    • pp.814-819
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    • 2006
  • This paper presents the impacts of Ultra Wide-Band(UWB) system applied in Indoor and Handhold communications using frequency band from 3.1 GHz to 10.6 GHz on Wireless Broad-band(WiBro) system based on Orthogonal Frequency Division Multiplexing(OFDM) using frequency of 2.3 GHz. The Minimum Coupling Loss(MCL) method for the case of single interference and Monte Carlo(MC) simulation for multiple interference considering practical scenario were used to evaluate the interference effects of UWB system on WiBro system. As a result, the minimum separation distance between single interferer and the victim receiver required 34.4 m and above to guarantee the co-existence. Also, the UWB transmitting PSD of around - 81 dBm / MHz below should be required to meet the minimum throughput loss of WiBro mobile station in case of multiple UWB interference.

Pharmacodynamics of CKD-602 (Belotecan) in 3D Cultures of Human Colorectal Carcinoma Cells

  • Lee Sin-Hyung;Al-Abd Ahmed M.;Park Jong-Kook;Cha Jung-Ho;Ahn Soon-Kil;Kim Joon-Kyum;Kuh Hyo-Jeong
    • Biomolecules & Therapeutics
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    • v.14 no.2
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    • pp.90-95
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    • 2006
  • CKD-602 exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vivo. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-l human colorectal cancer cells, respectively. The maximum effects($E_{max}$) induced by CKD-602 were significantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the $IC_{50's}$ of CKD-602 decreased to $23.5{\pm}1.0nM$ in monolayers after 24 h exposure and $42.3{\pm}1.7nM$ in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.