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Imidazole Antifungal Drugs Inhibit the Cell Proliferation and Invasion of Human Breast Cancer Cells

  • Bae, Sung Hun;Park, Ju Ho;Choi, Hyeon Gyeom;Kim, Hyesook;Kim, So Hee
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.494-502
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    • 2018
  • Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced $G_1$-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and $G_1$ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

Silencing of Mutant p53 Leads to Suppression of Human Breast Xenograft Tumor Growth in vivo (돌연변이 p53 단백질의 Silencing에 의한 사람유방암세포의 in vivo 항 종양 효과)

  • Park, Won Ick;Park, Se-Ra;Park, Hyun-Joo;Bae, Yun-Hee;Ryu, Hyun Su;Jang, Hye-Ock;Bae, Moon-Kyoung;Bae, Soo-Kyung
    • KSBB Journal
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    • v.31 no.1
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    • pp.52-57
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    • 2016
  • Mutant p53 (R280K) is highly expressed in MDA-MB-231 triple-negative human breast cancer cells. Currently, we reported the role of mutant p53-R280K in mediating the survival of MDA-MB-231 cells in vitro. The present study was undertaken to determine whether mutant p53-R280K affects breast cancer cell growth in vivo. To this end, we used small interfering RNA to knockdown the level of mutant p53-R280K in MDA-MB-231 cells. Silencing of mutant p53-R280K in MDA-MB-231 cells causes substantial tumor regression of established xenografts in vivo. In xenograft model for breast cancer, silencing of mutant p53-R280K in MDA-MB-231 cells significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in mutant p53-R280K silenced tumors compared to control. Our data indicate that mutant p53-R280K has an important role in mediating tumor growth of MDA-MB-231 cells in vivo. Taken together, this study suggests that endogenous mutant p53-R280K could be used as a therapeutic target for breast cancer cells harboring this TP53 missense mutation.

Docetaxel-loaded PLGA nanoparticles to increase pharmacological sensitivity in MDA-MB-231 and MCF-7 breast cancer cells

  • Tran, Phuong;Nguyen, Thu Nhan;Lee, Yeseul;Tran, Phan Nhan;Park, Jeong-Sook
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.5
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    • pp.479-488
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    • 2021
  • This study aimed to develop docetaxel (DTX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and -26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The in vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC50 values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

Chip Implementation of 830-Mb/s/pin Transceiver for LPDDR2 Memory Controller (LPDDR2 메모리 컨트롤러를 위한 830-Mb/s/pin 송수신기 칩 구현)

  • Jong-Hyeok, Lee;Chang-Min, Song;Young-Chan, Jang
    • Journal of IKEEE
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    • v.26 no.4
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    • pp.659-670
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    • 2022
  • An 830-Mb/s/pin transceiver for a controller supporting ×32 LPDDR2 memory is designed. The transmitter consists of eight unit circuits has an impedance in the range of 34Ω ∽ 240Ω, and its impedance is controlled by an impedance correction circuit. The transmitted DQS signal has a phase shifted by 90° compared to the DQ signals. In the receive operation, the read time calibration is performed by per-pin skew calibration and clock-domain crossing within a byte. The implemented transceiver for the LPDDR2 memory controller is designed by using a 55-nm process using a 1.2V supply voltage and has a maximum signal transmission rate of 830 Mb/s/pin. The area and power consumption of each lane are 0.664 mm2 and 22.3 mW, respectively.

Interleukin-9 Inhibits Lung Metastasis of Melanoma through Stimulating Anti-Tumor M1 Macrophages

  • Park, Sang Min;Do-Thi, Van Anh;Lee, Jie-Oh;Lee, Hayyoung;Kim, Young Sang
    • Molecules and Cells
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    • v.43 no.5
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    • pp.479-490
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    • 2020
  • Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4+ T cells, CD8+ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.

Effects of Curcuma longa L. on MDA-MB-231 Human Breast Cancer Cells and DMBA-induced Breast Cancer in Rats (울금이 MDA-MB-231 세포 및 DMBA로 유발된 흰쥐의 유방암에 미치는 영향)

  • Yang, Dong-Seon;Yang, Seung-Jeong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.3
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    • pp.44-58
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    • 2013
  • Objectives: Breast cancer is the most common cancer among women and has rapidly increasing rate annually. At present, western cancer therapies by surgery, radiation, and anticancer drug have not been fully effective. So many interests are given to herbal medicine on cancer treatment recently. This study was designed to investigate the effects of Curcuma longa L. (CL) on MDA-MB-231 human breast cancer cells and DMBA-induced breast cancer in rats. Methods: In this experiment, MDA-MB-231 cells were cultured in cell culture plates. 0.0625, 0.125, 0.25, 0.5, 1.0 mg/ml of CL extract were tested for their anti-proliferative effects on MDA-MB-231 cells by MMT assay. And we induced breast cancer in rats. The changes in tumor's weight, and the effects on proliferations of splenocyte and thymocyte were investigated. Results: CL showed anti-proliferative effects on MDA-MB-231 cells in proportion to concentration of the CL. DMBA-induced breast cancer in rats, tumor's weight of the rat was not statistically significant, but showed a tendency to be reduced in the groups treated with CL. Proliferation rate of the rat's splenocyte and thymocyte increased in proportion to CL. In breast cancer tissue, expression of ER-${\alpha}$ was weakened proportionately to the concentration of the CL. Conclusions: These data suggest that CL can prevent the proliferation of breast cancer, then CL is useful to treat patient with breast cancer.

Design of Efficient frequency Offset Estimator for MB-OFDM based UWB Systems (MB-OFDM 기반 UWB 시스템을 위한 효율적인 주파수 옵셋 추정기의 설계)

  • Kim, Kil-Hwan;Jung, Yun-Ho;Kim, Jae-Seok
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.34 no.3C
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    • pp.311-321
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    • 2009
  • This paper proposes an efficient frequency offset estimation algorithm for MB-OFDM based UWB systems. The time-frequency interleaving in MB-OFDM extends the time-interval between two transmitted OFDM symbols in the same sub-band. The extended time-interval causes not only the degradation of the system performance by reducing frequency offset estimation range, but also the increase of the hardware complexity by requiring the larger number of storing samples. The proposed estimation algorithm expands the estimation range by applying the proposed sign detection scheme. Simulation results show that the estimation range is increased above 30 ppm compared with a conventional auto-correlation based scheme. The estimation is performed on only one sub-band, and the frequency offsets of the others are calculated by relation to center frequency. This way reduced the number of the storing samples by about l/3. The frequency offset estimator with the proposed algorithm was designed into the architecture which minimizes hardware overhead by time-sharing operators and memory units, and which was synthesized to gate-level circuits using $0.13{\mu}m$ CMOS technology, and the total gates were about 47K.

A Study on Adsorption Characteristics of Natural Organic Matter and Taste & Odor Using Activated Carbon (활성탄 흡착지에서 응집조건에 따른 자연유기물질과 이·취미(Geosmin, 2-MIB) 파과특성에 관한 연구)

  • Kim, Sung-Jin;Hong, Seong-Ho;Shin, Heung-Sup
    • Journal of Korean Society of Water and Wastewater
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    • v.21 no.1
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    • pp.91-99
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    • 2007
  • It is well-known that the presence of NOM (natural organic matter) in water has a negative effect on removing taste and odor compounds by activated carbon adsorption. Therefore, various means such as enhanced coagulation are applied to reduce the NOM. The presence of taste & odor compounds in drinking water even parts per trillion, is enough to generate customer dissatisfaction. Therefore, the aim of this study was to evaluate carbon usage rate (CUR) for conventional coagulation (CC) and enhanced coagulation (EC) in order to improve the efficiency of adsorption of taste and odor compounds. Also, Effect of CC and EC on molecular weight fraction and the early stage breakthrough of 2-MIB and Geosmin are evaluated. When the enhanced coagulation was adapted for pretreatment for activated carbon adsorption the operation period could be prolonged by 3.5~4 times. CUR for CC was about 2 times greater than CUR for EC and this means that EC has more adsorption capacity than CC. To analyze effect of EC and CC on breakthrough of 2-MIB quantitatively, adsorbed NOM mass was calculated based on unit mass of activated carbon. In the early stage breakthrough of 2-MIB, total adsorbed NOM was 23.72mg/g for CC and 34.56mg/g for EC. Therefore, it is shown that the early breakthrough term of 2-MIB and Geosmin was improved due to increased adsorbability. The low-molecular-weight NOM (500~2000Da) compounds were the most competitive, participating in direct competition with 2-MIB for adsorption site.

An Ultra-High Speed 1.7ns Access 1Mb CMOS SRAM macro

  • T.J. Song;E.K. Lim;J.J. Lim;Lee, Y.K.;Kim, M.G.
    • Proceedings of the IEEK Conference
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    • 2002.07c
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    • pp.1559-1562
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    • 2002
  • This paper describes a 0.13um ultra-high speed 1Mb CMOS SRAM macro with 1.7ns access time. It achieves ultra-high speed operation using two novel approaches. First, it uses process insensitive sense amplifier (Double-Equalized Sense Amplifier) which improves voltage offset by about 10 percent. Secondly, it uses new replica-based sense amplifier driver which improves bit- line evaluation time by about 10 percent compared to the conventional technique. The various memory macros can be generated automatically by using a compiler, word-bit size from 64kb to 1 Mb including repairable redundancy circuits.

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The Design and Implementation of 802.1X Access Point Management System (802.1X Access Point 관리시스템의 설계 및 구현)

  • Ham, Young-Hwan;Chung, Byung-Ho;Chung, Kyo-Il
    • Proceedings of the Korea Information Processing Society Conference
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    • 2002.11b
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    • pp.1329-1332
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    • 2002
  • 최근에 공공장소에서의 보다 안정적이고 고속의 무선 인터넷 접속에 대한 욕구가 커지면서 무선랜에 대한 수요가 많아지고 있고, 유무선 사업자들은 무선랜 시장을 선점하기 위해서 서비스를 서두르고 있다. 이와 같은 무선랜환경에서 안전하게 사용자를 인증하고 서비스를 제공하기 위해서 802.1x 표준이 정의되었다. 이와 같은 802.1x 표준의 관리를 위한 MIB 구조가 IEEE 802.1x MIB에 정의되어 있다. 본 논문에서는 무선단말 사용자를 인증시켜 주고 무선랜서비스를 허가해주는 authenticator의 입장에서 AP를 관리하기 위한 관리 시스템을 위의 MIB 을 기준으로 해서 설계하고 구현하였다.

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