• 제목/요약/키워드: MCL1

검색결과 171건 처리시간 0.022초

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

  • 심용섭;이일규;조주필;민경일
    • 한국위성정보통신학회논문지
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    • 제6권1호
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    • pp.63-67
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    • 2011
  • 본 논문은 MCL(Minimum Coupling Loss)와 MC(Monte-Carlo) 방법을 이용하여 같은 주파수를 사용하는 ISM(Industrial Scientific Medical) 기기와 무선랜이 공간적으로 인접하여 사용될 경우의 간섭 영향 분석을 통해 ISM 기기로부터 무선랜을 보호하기 위한 보호 거리를 제시하였다. CISPR(International Special Committee on Radio Interference)에서 규정한 ISM 기기의 기준치를 간섭 파워로 설정하여 ISM 기기로부터 무선랜을 보호하기 위한 보호 거리를 산출하였다. 그 결과 최악의 상황을 고려한 MCL 분석시 105 m의 보호 거리와 통계적 간섭 확률을 바탕으로 한 MC 분석시 17 m의 보호 거리가 각각 산출되었다.

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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    • 제35권7호
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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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    • 제13권7호
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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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    • 제14권6호
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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.

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

  • 백문승;문성규;이미지;김승우
    • 대한두경부종양학회지
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    • 제37권1호
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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.

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

  • 김재석;이민정;이창민;이상화;배외식;곽종영
    • 생명과학회지
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    • 제12권4호
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    • pp.452-459
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    • 2002
  • 호중의 세포사멸은 자연적으로 일어나지만 여러 자극에 의한 신호에 의하여 증가하거나 지연된다. 본 연구에서는 세포 내 단백질 분비과정을 억제한다고 알려진 BFA가 호중구의 자연 세포사멸 및 세포사멸 지연에 어떠한 기작으로 작용하는가를 연구하였다. 호중구의 세포사멸은 사람 말초 혈액으로부터 분리하여 세포 배양 20시간 후 형태 변화, annexin V and propidium iodide의 염색, 및 DNA 전기영동 등으로 조사하였다. BFA는 농도 의존형으로 호중구의 세포사멸을 증가시킨다. CM-CSF나 LPS에 의한 세포사멸의 지연도 BFA에 의하여 억제되었다. 그러나 BFA의 영향은 db-cAMP, dexamethasone, 및 IL-8을 처리한 세포에서는 큰 영향을 받지 않았다. PKC-5의 억제제인 rottlerin에 의한 세포사멸의 지연은 BFA에 의하여 감소하였다. 그러나 BFA에 의한 세포사멸의 유도는 caspase-3 억제제인 zDEVD-fmk에 의하여는 영향을 받지 않았다. 한편, 세포사멸 억제에 관여하는 Mcl-1 단백질의 발현은 BFA의 처리에 의하여 감소하였다. 이들 결과들은 세포 내 단백질 분비 과정의 억제가 호중구의 세포사멸에 관여하며 이들의 작용은 Mcl-1 발현의 조절에 의한다는 것을 제시하고 있다.

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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    • 제37권3호
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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)

  • 우희권;한미경;조은정;정일남
    • Bulletin of the Korean Chemical Society
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    • 제16권1호
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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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    • 제16권2호
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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.

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

  • 우상희;이선희;이영하
    • 미생물학회지
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    • 제52권4호
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    • pp.455-462
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    • 2016
  • Pseudomonas aeruginosa P-5 균주는 홀수개의 탄소수를 갖는 지방산으로부터 3-hydroxyvalerate (3HV)와 medium-chain-length (MCL) 3-hydroxyalkanoates (3HAs) 단위체로 구성된 popolyhydroxyalkanoate (PHA) 공중합체를 생산하는 특이한 성질을 갖고 있다. 이 균주가 갖고 있는 2개의 MCL-PHA synthases ($PhaC1_{P-5}$$PhaC2_{P-5}$)의 탄소길이에 따른 기질특이성을 비교하기 위하여 각각의 유전자를 PHA 생합성능이 결여된 돌연변이주 Pseudomonas putida GPp104에 도입하고 발현시킨 결과, $PhaC2_{P-5}$는 3HV와 MCL 3HAs로 이루어진 공중합체를 생산하지만 $PhaC1_{P-5}$는 단지 MCL 3HAs로 구성된 공중합체를 생산하였다. 이는 $PhaC2_{P-5}$$PhaC1_{P-5}$과는 달리 보다 짧은 탄소길이의 3-hydroxyvaleryl Co-A를 기질로 인지하여 합성반응에 이용할 수 있음을 보여주는 것이다. 또한 $PhaC2_{P-5}$의 효소활성 및 기질특이성의 변화를 유도하기 위하여 위치지정 돌연변이생성을 수행하고 P. putida GPp104과 다른 PHA 생합성능 결여 돌연변이주인 Ralstonia eutropha $PHB^-4$에서 발현시킨 결과, $PhaC2_{P-5}$ 내 두 개 아미노산의 치환(Ser326Thr과 Gln482Lys)이 공중합체의 3HV 함량을 크게 증진시키는 효과를 보였다. 두 개 아미노산이 모두 치환된 $PhaC2_{P-5}$ 유전자($phaC2_{P-5}QKST$)를 갖는 P. putida GPp104를 nonanoic acid가 탄소원으로 함유된 배지에서 배양하였을 때, 모균주에 비해 공중합체 함량과 공중합체 내 3HV 함량이 각각 2.5배 및 3.5배 증가하였다. 따라서 $phaC2_{P-5}QKST$를 포함하는 재조합 균주는 개량된 물성의 신규PHAs 생산에 유용할 것으로 기대된다.