• Title/Summary/Keyword: MCL1

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Study on Compatibility between ISM Equipment and WLAN (ISM 기기와 무선랜의 양립성에 관한 연구)

  • Shim, Yong-Sup;Lee, Il-Kyoo;Cho, Ju-Phil;Min, Kyoung-Il
    • Journal of Satellite, Information and Communications
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    • v.6 no.1
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    • pp.63-67
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    • 2011
  • This paper analyzes the interference effect of ISM(Industrial Scientific Medical) equipment on WLAN in order to protect WLAN in interference environment which WLAN Station is close to ISM equipment. CISPR(International Special Committee on Radio Interference) radiation limit standard was used for interfering power of ISM equipment. Then, MCL(Minimum Coupling Loss) which is for the worst case and MC(Monte Carlo) which is based on statistic interference probability are used to get protection distance. As a result, the protection distance of 105 m was calculated by using MCL for the worst case. And, the protection distance of 17 m was calculated by using MC for statistic analysis.

A Combined Pharmacophore-Based Virtual Screening, Docking Study and Molecular Dynamics (MD) Simulation Approach to Identify Inhibitors with Novel Scaffolds for Myeloid cell leukemia (Mcl-1)

  • Bao, Guang-Kai;Zhou, Lu;Wang, Tai-Jin;He, Lu-Fen;Liu, Tao
    • Bulletin of the Korean Chemical Society
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    • v.35 no.7
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    • pp.2097-2108
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    • 2014
  • Chemical feature based quantitative pharmacophore models were generated using the HypoGen module implemented in DS2.5. The best hypothesis, Hypo1, which was characterized by the highest correlation coefficient (0.96), the highest cost difference (61.60) and the lowest RMSD (0.74), consisted of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic and one ring aromatic. The reliability of Hypo1 was validated on the basis of cost analysis, test set, Fischer's randomization method and GH test method. The validated Hypo1 was used as a 3D search query to identify novel inhibitors. The screened molecules were further refined by employing ADMET, docking studies and visual inspection. Three compounds with novel scaffolds were selected as the most promising candidates for the designing of Mcl-1 antagonists. Finally, a 10 ns molecular dynamics simulation was carried out on the complex of receptor and the retrieved ligand to demonstrate that the binding mode was stable during the MD simulation.

Oxaliplatin Sensitizes OS Cells to TRAIL-induced Apoptosis Via Down-regulation of Mcl1

  • Huang, Tao;Gong, Wei-Hua;Li, Xiu-Cheng;Zou, Chun-Ping;Jiang, Guang-Jian;Li, Xu-Hui;Qian, Hao
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3477-3481
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    • 2012
  • Purpose: To investigate the killing effect on OS cells of a combination of oxaliplatin and TRAIL and related molecular mechanisms. Methods: TRAIL and oxaliplatin were applied to OS732 cells singly or jointly and survival inhibition rates were measured by MTT assay, changes of cellular shape being assessed with inverted phase contrast and fluorescence microscopy. Apoptotic rates were analyzed by flow cytometry (FCM) and immunocytochemistry was used to examine Mcl1 expression of OS732 cells. Results: The survival inhibition rate of combined application of $100{\mu}g/ml$ TRAIL and $1{\mu}g/ml$ oxaliplatin on OS-732 cells was significantly higher than that of either agent singly (p<0.01). Changes of cellular shape and apoptotic rates also indicated apoptosis-inducing effects of combined application to be much stronger than those of individual application. Oxaliplatin had the effect of down-regulating Mcl1 expression and sensitizing OS cells to TRAIL-induced apoptosis. Conclusion: A combination of TRAIL and oxaliplatin exerts strong killing effects on OS-732 cells which might be related to down-regulation of Mcl1 expression.

Simultaneous Inhibition of CXCR4 and VLA-4 Exhibits Combinatorial Effect in Overcoming Stroma-Mediated Chemotherapy Resistance in Mantle Cell Lymphoma Cells

  • Kim, Yu-Ri;Eom, Ki-Seong
    • IMMUNE NETWORK
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    • v.14 no.6
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    • pp.296-306
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    • 2014
  • There is growing evidence that crosstalk between mantle cell lymphoma (MCL) cells and stromal microenvironments, such as bone marrow and secondary lymphoid tissues, promotes tumor progression by enhancing survival and growth as well as drug resistance of MCL cells. Recent advances in the understanding of lymphoma microenvironment have led to the identification of crucial factors involved in the crosstalk and subsequent generation of their targeted agents. In the present study, we evaluated the combinatory effect of blocking antibodies (Ab) targeting CXCR4 and VLA-4, both of which were known to play significant roles in the induction of environment-mediated drug resistance (EMDR) in MCL cell line, Jeko-1. Simultaneous treatment with anti-CXCR4 and anti-VLA-4 Ab not only reduced the migration of Jeko-1 cells into the protective stromal cells, but also enhanced sensitivity of Jeko-1 to a chemotherapeutic agent to a greater degree than with either Ab alone. These combinatorial effects were associated with decreased phosphorylation of ERK1/2, AKT and NF-${\kappa}B$. Importantly, drug resistance could not be overcome once the adhesion of Jeko-1 to the stromal occurred despite the combined use of Abs, suggesting that the efforts to mitigate migration of MCLs should be attempted as much as possible. Our results provide a basis for a future development of therapeutic strategies targeting both CXCR4 and VLA-4, such as Ab combinations or bispecific antibodies, to improve treatment outcomes of MCL with grave prognosis.

A Case of Blastoid Mantle Cell Lymphoma Occurring in the Parotid Gland (이하선에 발생한 아구양 외투세포 림프종 1예)

  • Beag, Moon Seung;Moon, Seong Kyu;Lee, Mi Ji;Kim, Seung Woo
    • Korean Journal of Head & Neck Oncology
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    • v.37 no.1
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    • pp.23-27
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    • 2021
  • Mantle cell lymphoma (MCL) is a rare subtype of B-cell neoplasm and it accounts for about 3~6% of all non-Hodgkin's lymphomas. It occurs mainly in middle-aged or elderly man, involving the extra-nodal sites such as gastrointestinal tract, bone marrow and Waldeyer's ring. The incidence of the MCL in salivary gland is about 3%. The blastoid MCL is a rare variant and it has a very aggressive clinical course. It is extremely rare to be arising from the parotid gland. To our knowledge, similar case has not been reported in domestic literature, one case has been described in English literature. We experienced a rare and unique disease entity and report it with brief literature review.

Effects of brefeldin A on spontaneous and delayed apoptosis of human neutrophils (호중구의 자연 세포사멸 및 세포사멸 지연에 대한 Brefeldin A의 영향)

  • 김재석;이민정;이창민;이상화;배외식;곽종영
    • Journal of Life Science
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    • v.12 no.4
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    • pp.452-459
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    • 2002
  • Neutrophil apoptosis is a constitutive process that can be enhanced or delayed by various stimuli. In this study, effect of brefeldin A (BFA), which affects biological process of secretion, on constitutive and delayed apoptosis of neutrophils was investigated. Neutrophil apoptosis was determined after culturing for 20 hr in vitro by morphological changes, annexin V staining and DNA electrophoresis. BFA increased the constitutive apoptotic rate of neutrophils in dose-dependent manner. The delay of apoptosis induced by granulocyte macrophage-colony stimulating factor and lipopolysaccharide was also blocked by 10 $\mu$M of BFA. However, this effect of BFA was less marked when neutrophils were treated with dexamethasone, interleukin-8, or dibutyryl-cAMP. Moreover, the delay of neutrophil apoptosis induced by rottlerin, a specific inhibitor of protein kinase C-$\delta$ was significantly abrogated by BFA. Although BFA-induced apoptosis was not blocked by the caspase-3 inhibitor, zDEVD-fmk, expression levels of myeloid cell leukemia-1 (Mcl-1) were down-regulated by BFA. These results suggest that derangement of vesicular protein transport may be involved in the apoptosis of neutrophils, and that the action of BFA on apoptosis is dependent on changes in the expression of Mcl-1.

A Conserved Mechanism for Binding of p53 DNA-Binding Domain and Anti-Apoptotic Bcl-2 Family Proteins

  • Lee, Dong-Hwa;Ha, Ji-Hyang;Kim, Yul;Jang, Mi;Park, Sung Jean;Yoon, Ho Sup;Kim, Eun-Hee;Bae, Kwang-Hee;Park, Byoung Chul;Park, Sung Goo;Yi, Gwan-Su;Chi, Seung-Wook
    • Molecules and Cells
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    • v.37 no.3
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    • pp.264-269
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    • 2014
  • The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. In this study, we investigated the binding of p53 DNA-binding domain (p53DBD) with the anti-apoptotic Bcl-2 family proteins, Bcl-w, Mcl-1, and Bcl-2, using GST pull-down assay and NMR spectroscopy. The GST pull-down assays and NMR experiments demonstrated the direct binding of the p53DBD with Bcl-w, Mcl-1, and Bcl-2. Further, NMR chemical shift perturbation data showed that Bcl-w and Mcl-1 bind to the positively charged DNA-binding surface of p53DBD. Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. Furthermore, the chemical shift perturbations on Bcl-w, Mcl-1, and Bcl-2 induced by p53DBD binding occurred not only at the p53DBD-binding acidic region but also at the BH3 peptide-binding pocket, which suggests an allosteric conformational change similar to that observed in Bcl-$X_L$. Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53.

Dehydrogenative Polymerization of New Alkylsilanes Catalyzed by $Cp_2MCl_2$/Red-Al System (M=Ti, Hf): Synthesis of Poly(substituted 3-phenyl-1-silabutanes)

  • U, Hui Gwon;Han, Mi Gyeong;Jo, Eun Jeong;Jeong, Il Nam
    • Bulletin of the Korean Chemical Society
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    • v.16 no.1
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    • pp.58-62
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    • 1995
  • Substituted 3-phenyl-1-silabutanes such as 3-phenyl-1-silabutane (1), 3-(2,5-dimethylphenyl)-1-silabutane (2), 3-(p-chlorotolyl)-1-silabutane (3), and 3-naphthyl-1-silabutane (4) were prepared in 62-96% yield by reduction of the corresponding substituted 3-phenyl-1,1-dichloro-1-silabutanes with LiAlH4. The dehydrogenative polymerization of the monomer silanes was carried out with Cp2MCl2/Red-Al (M=Ti, Hf) catalyst system. The molecular weight of the polymers produced ranged from 700 to 1300 (vs polystyrene) with degree of polymerization (DP) of 5 through 16 and with polydispersity index (PDI)=1.1-2.1. The dehydrogenative polymerization of the monomer silanes with Cp2TiCl2/Red-Al catalyst system occurred at a faster rate and produced somewhat higher molecular weights of polysilane than that with Cp2HfCl2/Red-Al catalyst system.

Dehydrogenative Polymerization of New Alkylsilanes Catalyzed by $Cp_2MCl_2$/Red-Al System (M=Ti, Hf)

  • 우희권;김숙연;조은정;정일남
    • Bulletin of the Korean Chemical Society
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    • v.16 no.2
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    • pp.138-143
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    • 1995
  • Substituted 3-phenyl-1-silabutanes, 3-chlorophenyl-1-silabutane (1), 3-tolyl-1-silabutane (2), and 3-phenoxyphenyl-1-silabutane (3), were prepared in 68-98% yield by reduction of the corresponding substituted 3-phenyl-1,1-dichloro-1-silabutanes with LiAlH4. The dehydrogenative homopolymerization and copolymerization of the silanes were performed with Cp2MCl2/Red-Al (M=Ti, Hf) catalyst system. The molecular weights of the resulting polymers were in the of range 600 to 1100 (vs polystyrene) with degree of polymerization (DP) of 5 to 8 and polydispersity index (PDI) of 1.6 to 3.8. The monomer silanes underwent the dehydrogenative polymerization with Cp2TiCl2/Red-Al catalyst to produce somewhat higher molecular weight polysilanes compared with Cp2HfCl2/Red-Al catalyst.

Substrate chain-length specificities of polyhydroxyalkanoate synthases PhaC1 and PhaC2 from Pseudomonas aeruginosa P-5 (Pseudomonas aeruginosa P-5에 존재하는 polyhydroxyalkanoate synthase PhaC1과 PhaC2의 기질특이성)

  • Woo, Sang Hee;Lee, Sun Hee;Rhee, Young Ha
    • Korean Journal of Microbiology
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    • v.52 no.4
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    • pp.455-462
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    • 2016
  • Pseudomonas aeruginosa P-5 is an unusual organism capable of synthesizing polyhydroxyalkanoates (PHAs) consisting of 3-hydroxyvalerate (3HV) and medium-chain-length (MCL) 3-hydroxyalkanoate (3HA) monomer units when C-odd alkanoic acids are fed as the sole carbon source. Evaluation of the substrate chain-length specificity of two P. aeruginosa P-5 PHA synthases ($PhaC1_{P-5}$ and $PhaC2_{P-5}$) by heterologous expression of $PhaC1_{P-5}$ and $PhaC2_{P-5}$ genes in Pseudomonas putida GPp104 revealed that $PhaC2_{P-5}$ incorporates both 3HV and MCL 3HAs into PHA, whereas $PhaC1_{P-5}$ favors only MCL 3HAs for polymerization. In order to obtain $PhaC2_{P-5}$ mutants with altered substrate specificity, site-specific mutagenesis for $PhaC2_{P-5}$ was conducted. Amino acid substitutions of $PhaC2_{P-5}$ at two positions (Ser326Thr and Gln482Lys) were very effective for synthesizing copolymers with a higher 3HV fraction. When recombinant P. putida GPp104 harboring double mutated $phaC2_{P-5}$ gene ($phaC2_{P-5}QKST$) was grown on nonanoic acid, 2.5-fold increase of copolymer content with 3.8-fold increase of 3HV fraction was observed. The $phaC2_{P-5}QKST$-containing Ralstonia eutropha PHB-4 supplemented with valeric acid also produced copolymers consisting of 3HV and 3-hydroxyheptanoate with a high 3HV fraction. These results suggest that recombinants containing $phaC2_{P-5}QKST$ could be useful for production of new PHA copolymers with improved material properties.