• Title/Summary/Keyword: Cell protection

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Why a Combination of WP 631 and Epo B is an Improvement on the Drugs Singly - Involvement in the Cell Cycle and Mitotic Slippage

  • Bukowska, Barbara;Rogalska, Aneta;Forma, Ewa;Brys, Magdalena;Marczak, Agnieszka
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1299-1308
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    • 2016
  • Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

Design of Low-Area 1-kb PMOS Antifuse-Type OTP IP (저면적 1-kb PMOS Antifuse-Type OTP IP 설계)

  • Lee, Cheon-Hyo;Jang, Ji-Hye;Kang, Min-Cheol;Lee, Byung-June;Ha, Pan-Bong;Kim, Young-Hee
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.13 no.9
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    • pp.1858-1864
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    • 2009
  • In this paper, we design a non-volatile memory IP, 1-kb one-time programmable (OTP) memory, used for power management ICs. Since a conventional OTP cell uses an isolated NMOS transistor as an antifuse, there is an advantage of it big cell size with the BCD process. We use, therefore, a PMOS transistor as an antifuse in lieu of the isolated NMOS transistor and minimize the cell size by optimizing the size of a OTP cell transistor. And we add an ESD protection circuit to the OTP core circuit to prevent an arbitrary cell from being programmed by a high voltage between the terminals of the PMOS antifuse when the ESD test is done. Furthermore, we propose a method of turning on a PMOS pull-up transistor of high impedance to eliminate a gate coupling noise in reading a non-programmed cell. The layout size of the designed 1-kb PMOS-type antifuse OTP IP with Dongbu's $0.18{\mu}m$ BCD is $129.93{\times}452.26{\mu}m^2$.

CELL MORPHOLOGY CHANGE BY THE ULTRAVIOLET RAY IRRADIATION

  • Park, Myoung-Joo;Matuo, Yoichirou;Akiyama, Yoko;Izumi, Yoshinobu;Nishijima, Shigehiro
    • Journal of Radiation Protection and Research
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    • v.34 no.1
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    • pp.15-24
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    • 2009
  • The effect of low doses of ultraviolet (UV) irradiation on morphology changes of cell has been studied based on the observation of the cell length. It was shown that UV-irradiated cell has different behavior in comparison with non-irradiated cell. From the histogram of cell-length distribution, it was confirmed that cell cycle of non irradiated cell was 28 hours, and that cell cycle of irradiated cell with dose of $20\;Jm^{-2}$ was delayed (39 hours), while irradiated cell with $40\;Jm^{-2}$ and $60\;Jm^{-2}$ did not divide and kept growing continuously. It was supposed that in case of $20\;Jm^{-2}$ of irradiation dose, the cell cycle was delayed because the checkpoint worked in order to repair DNA damage induced by generation of pyrimidine dimer, reactive oxygen species and so on. It was also supposed that in case of $40\;Jm^{-2}$ and $60\;Jm^{-2}$ of irradiation dose, overgrowth was induced because the checkpoint was not worked well. The morphology of overgrown cell was similar to that of normally senescent cell. Therefore, it was considered that cell senescence was accelerated by UV irradiation with irradiation doses of $40\;Jm^{-2}$ and $60\;Jm^{-2}$.

[ $A_1$ ] Receptor-mediated Protection against Amyloid Beta-induced Injury in Human Neuroglioma Cells

  • Cho, Yong-Woon;Jung, Hyun-Ju;Kim, Yong-Keun;Woo, Jae-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.2
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    • pp.37-43
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    • 2007
  • Adenosine has been reported to provide cytoprotection in the central nervous systems as well as myocardium by activating cell surface adenosine receptors. However, the exact target and mechanism of its action still remain controversial. The present study was performed to examine whether adenosine has a protective effect against $A{\beta}$-induced injury in neuroglial cells. The astrocyte-derived human neuroglioma cell line, A172 cells, and $A{\beta}_{25{\sim}35}$ were employed to produce an experimental $A{\beta}$-induced glial cell injury model. Adenosine significantly prevented $A{\beta}$-induced apoptotic cell death. Studies using various nucleotide receptor agonists and antagonists suggested that the protection was mediated by $A_1$ receptors. Adenosine attenuated $A{\beta}$-induced impairment in mitochondrial functional integrity as estimated by cellular ATP level and MTT reduction ability. In addition, adenosine prevented $A{\beta}$-induced mitochondrial permeability transition, release of cytochrome c into cytosol and subsequent activation of caspase-9. The protective effect of adenosine disappeared when cells were pretreated with 5-hydroxydecanoate, a selective blocker of the mitochondrial ATP-sensitive $K^+$ channel. In conclusion, therefore we suggest that adenosine exerts protective effect against $A{\beta}$-induced cell death of A172 cells, and that the underlying mechanism of the protection may be attributed to preservation of mitochonarial functional integrity through opening of the mitochondrial ATP-sensitive $K^+$ channels.

Functional Gene Analysis for the Protection of Male Germ Cell Injury Induced by Busulfan Treatment using cDNA Microarray Analysis

  • 최윤정;옥도원;황규찬;김진회
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.21-21
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    • 2003
  • Male germ cell apoptosis has been extensively explored in rodent. In contrast, very little is known about their susceptibility to apoptosis stimuli of developing germ cell stages at the time when germ cell depletion after busulfan treatment occurs. Furthermore, it is still unanswered how spermatogonial stem cells are resistant to busulfan treatment. We examined the change of gene expression in detail using cDNA microarray analysis of mouse testis treated with busulfan. A subtoxic dose of busulfan (40mg/kg of body weight) transiently increased 228 mRNA levels among of the 8000 genes analyzed. TagMan analysis confirmed that the mRNA levels such as defensive protein, support protein, enzymatic protein, transport protein, and hormonal protein were rapidly increased. These results were re-confirmed by real-time PCR analysis. However, the expression levels of these genes induced by busulfan treatment were significantly reduced in control testis, indicating that both of male germ cells and somatic cells after busulfan treatment induces self-defense mechanism for protection of testicular cell death. Among them, we conclude that defense proteins play a key role in testis injury induced by busulfan.

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Radiation-induced Cochlea Hair Cell Death: Mechanisms and Protection

  • Tan, Pei-Xin;Du, Sha-Sha;Ren, Chen;Yao, Qi-Wei;Yuan, Ya-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5631-5635
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    • 2013
  • Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini-review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC), are claimed to be effective at reducing radiation-inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre-examined in order to minimize the damage to cochlea hair cells.

Effect of Pyunggangaeuljihyul-tang (Pinggankaiyuzhixue-tang) on Toxic Agent Induced Liver Cell Damage (평간개울지혈탕이 독성약물에 의한 간조직 손상에 미치는 영향)

  • 오세광;김원일;김우환
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.96-107
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    • 2003
  • Objective : This study was undertaken to determine if Pyunggangaeuljihyul-tang (Pinggankaiyuzhixue-tang, PG) has a protective effect against cell injury induced by various toxic agents in rabbit liver, Methods : Cell injury in vitro was estimated by measuring lactate dehydrogenase (LDH), and that in vivo was estimated by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in serum. Lipid peroxidation was examined by measuring malondialdehyde, a product of lipid per oxidation. Results : PG prevented the LDH release by $CCl_4$, mercury, menadione, and tert-butyl hydroperoxide treatment in vitro in liver slices. The extent of protection by 2% PG was similar to that of $10{\mu\textrm{M}}$ N,N'-diphenyl-p-phenylenedianline, a potent antioxidant, in tert-butyl hydroperoxide-induced LDH release. PG also prevented lipid peroxidation and depletion of cellular ATP induced by Hg. Hg causes motphological changes including cell necrosis and its effect was significantly prevented by PG. When rats were treated intraperitoneatly with 0.5 ml/kg of $CCl_4$, serum alanine aminotransferase and aspartate aminotransferase activities were increased compared with the control, which was significantly inhibited by pretreatment of PG. PG also prevented reduction in GSH and lipid peroxidation induced by $CCl_4$ Conclusion : These results suggest that PG exerts aprotective effect against various toxic agents by its antioxidant action in liver tissues. Thus, PG may be used in prevention and treatment of drug-induced liver cell injury. However, the precise mechanisms of PG protection remain to be determined.

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The Method Effect of Reinforced Concrete by Applying Impressed Current Cathodic Protection (외부전원법을 적용한 철근콘크리트의 방식효과)

  • Lee, Hae-Seung;Cho, Gyu-Hwan;Park, Dong-Cheon
    • Proceedings of the Korean Institute of Building Construction Conference
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    • 2013.11a
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    • pp.60-61
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    • 2013
  • For reinforced concrete structures located in a sea environment, the Impressed Current Cathodic Protection (ICCP) is mostly used as a signature method to prevent steel corrosion. For this research, specimens to which the ICCP is applied were manufactured under the assumption of two following cases the specimens are exposed to various salt damage environments (submerged zone, tidal zone), and deteriorative factors (crack) occur in concrete. For the specimens manufactured, an enhancement experiment for deterioration was conducted through regular cycle change under the temperature between 15 ~ 70℃ with 70 ~ 90% humidity. Afterwards, the method effect was verified through a half-cell method and application of the ICCP derived from salt damage environments was investigated.

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RADIOPROTECTIVE EFFECT OF ALGIN-OLIGOSACCHARIDE THROUGH MEASURING CASPASE-3 AND CASPASE-9 IN MICE

  • Choi, Seong-Kwan;Jung, Woon-Kwan;Lee, Kyu-Soo;Jang, Young-Il;Dong, Kyeong-Rae
    • Journal of Radiation Protection and Research
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    • v.32 no.4
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    • pp.134-139
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    • 2007
  • In order to find out the Radioprotective effect of algin-oligosaccharide(AOS), this study, with a mouse of which whole frame irradiated by 3 Gy radiation once, measured caspase-3 and caspase-9 amid cell signaling connected to apoptosis in order to observe cell activation. In Caspase-3 and Caspase-9 test for observing cell activation, both of Caspase-3 and Caspase-9 showed highly increased O.D. value in the irradiation control group, while the whole groups treated with algin-oligosaccharide before or after irradiation indicated lower O.D. value than the irradiation control group, especially showed big difference in 7 day's treatment group of before irradiation (P<0.001). It confirmed that Caspase generation was restrained in AOS treatment group. Consequently, this study inquired into the fact that algin-oligosaccharide with superior antioxidant activity performed radiation protection by inducing restraint of Caspase generation and confirmed that natural product with less chemical toxicity was able to be applied as radioprotector.

Research on Standards for Protection against Electric Shock in Global Technical Regulations of Fuel Cell Vehicle (연료전지 자동차 세계기술규정의 감전보호기준 연구)

  • HwangBo, Cheon;Lee, Kyu-Myong;You, Kyeong-Jun
    • Transactions of the Korean hydrogen and new energy society
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    • v.21 no.3
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    • pp.167-183
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    • 2010
  • This paper analyzes the backgrounds of the standards for protection against electric shock in Global Technical Regulations (GTR) of Fuel Cell Vehicle (FCV). Targets on research were high voltage criteria, safety current, isolation and grounding resistance, time limitation, energy, adequate clearance, and test procedure. Based on human impedance and effect of current in IEC 60479-1, safety of human was examined. Then, isolation and grounding circuit model of FCV were analyzed theoretically. The results give several suggestions: touch voltage less than 25V, AC energy less than 0.0813J, separation considering middle finger length, grounding resistance less than $0.2\Omega$, maximum AC ground voltage of 1V (rms), and isolation resistance between earth and electrical chassis. In MATLAB/Simulink environment, error characteristics of isolation resistance measurement procedure using internal DC sources were analyzed under variations of internal resistance of voltmeter and isolation resistance.