• Title/Summary/Keyword: survival signal

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The Signaling Mechanism of TGF-β1 Induced Bovine Mammary Epithelial Cell Apoptosis

  • Di, He-Shuang;Wang, Li-Gang;Wang, Gen-Lin;Zhou, Lei;Yang, Yuan-Yuan
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.3
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    • pp.304-310
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    • 2012
  • The present study showed that Transforming growth factor beta 1 (TGF-${\beta}_1$) can induce apoptosis of bovine mammary epithelial cells. This apoptosis was also observed with phosphorylation of Smad2/3 within 0.5-2 h. Afterwards the signal transferred into the nucleus. Moreover, intracellular free $Ca^{2+}$ concentration was significantly elevated as well as Caspase-3 activated and DNA lysised, thereby inducing the programmed cell death. This signaling pathway of TGF-${\beta}_1$ was blocked by SB-431542 ($10^{-2}{\mu}M$) via inhibiting ALK-5 kinase activity, which thus reversed the anti-proliferation and apoptosis effect of TGF-${\beta}_1$ in mammary epithelial cells. These results indicated that TGF-${\beta}_1$ induced apoptosis of bovine mammary epithelial cells through the ALK-5-Smad2/3 pathway, which plays an important role in inhibiting survival of mammary epithelial cells. Moreover, intracellular $Ca^{2+}$ also played a critical role in TGF-${\beta}_1$-induced cell apoptosis.

Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

  • Zheng, De-Jie;Yu, Guo-Hua;Gao, Jian-Feng;Gu, Jun-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4485-4494
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    • 2013
  • Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

Effect of Lycii cortex radicis Extraction on Glioma Cell Viability

  • Kim, Seang-Jae;Jeong, Ji-Cheon
    • The Journal of Korean Medicine
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    • v.30 no.6
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    • pp.17-26
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    • 2009
  • Objectives: Little information is available regarding the effect of Lycii cortex radicis (LCR) on cell viability in glioma cells. This study was therefore undertaken to examine the effect of LCR on cell survival in U87MG human glioma cells. Methods: Cell viability and cell death were estimated by MTT assay and trypan blue exclusion assay, respectively. Reactive oxygen species (ROS) generation was measured using the fluorescence probe DCFH-DA. Activation of Akt and extracellular signal-regulated kinase (ERK) and activation of caspase-3 were estimated by Western blot analysis. Results: LCR resulted in apoptotic cell death in a dose- and time-dependent manner. LCR increased reactive oxygen species (ROS) generation and LCR-induced cell death was also prevented by antioxidants, suggesting that ROS generation played a critical role in LCR-induced cell death. Western blot analysis showed that LCR treatment caused down-regulation of Akt and ERK. The LCR-induced cell death was increased by the inhibitors of Akt and ERK. Activation of caspase-3 was stimulated by LCR and caspase inhibitors prevented the LCR-induced cell death. Conclusion: These findings suggest that LCR results in human glioma cell death through a mechanism involving ROS generation, down-regulation of Akt and ERK, and caspase activation.

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Cytosine Arabinoside-Induced PC12 Cell Death Pathway (Cytosine Arabinoside 유도된 PC12 세포의 사망 경로)

  • Yang, Bo-Gee;Yang, Byung-Hwan;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.5 no.2
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    • pp.219-226
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    • 1998
  • Cytosine arabinoside(AraC) inhibits DNA synthesis and ${\beta}$-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

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Comparison of the Nucleotide Sequence of Cloned Osteopontin from Hanwoo and Holstein

  • Lee, Tae Young;Ju, Sung Kyu;Nam, Myoung Soo
    • Food Science of Animal Resources
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    • v.33 no.3
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    • pp.331-334
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    • 2013
  • Osteopontin (OPN) is a secreted phosphorylated glycoprotein. It has an important role in multiple biological processes including cell survival, bone remodeling, inhibition of ectopic calcification, as well as, is thought to have potential immune modulation activities. In this work, we isolated and characterized a full-length open reading frame (ORF) of Korean native cow's OPN from Korean native cow's (Hanwoo) kidney, and successfully cloned firstly on Hanwoo's OPN. The sequencing results indicated that the isolated cDNA was 1190 bp in length containing a complete ORF of 837 bp. It encoded a precursor protein Hanwoo's OPN consisting of 278 amino acids with a signal peptide of 16 amino acids. Amino acid homology was found to be 99.3% as compared to the corresponding sequences of Holstein bone marrow OPN. Hanwoo's kidney OPN and Holstein bone marrow OPN are different only in two amino acid residues 42 and 56, amino acid residue 42 is Thr (T) ${\leftrightarrow}$ Ile (I), and amino acid residue 56 is Ala (A) ${\leftrightarrow}$ Thr (T) respectively. These results from the present work would be helpful to elucidate the biological function of Hanwoo's OPN and provided a foundation for further insight into role of Hanwoo's OPN.

Study on trends of cancer study in TKM and its research strategy in future (한의학계(韓醫學界)의 암연구동향(癌硏究動向)과 연구(硏究) 전략(戰略)에 대한 연구(硏究))

  • Kim, Sung-Hoon
    • The Journal of Korean Medicine
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    • v.19 no.1
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    • pp.470-499
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    • 1998
  • For the purpose of designing more successful cancer research, the strategy for cancer study in the field of Traditional Korean Medicine(TKM) during the 21th century was examined from the analysis of trends on cancer study in traditional korean medicine. The results were summarized as follows: 1. So far cancer research in TKM was chiefly done on cytotoxicity, side-effects by chemotherapy, tumor immunology, apoptosis, survival time with S-180 and pulmonary colonization assay and also clonogenic assay, cell adhesion assay, angiogenesis, cell-differentiation and side-effect by radiotherapy were partly performed. 2. It may be ideal that we should study synergistic effect between constituent drugs of prescriptions, tumor immunology, combined therapy between western and oriental medicines by reducing side-effect by radiotherapy and chemotherapy and antimetastasis according to the characteristics of oriental medicine chiefly and also supplement the studies on molecular biology, gene therapy, angiogensis and signal transduction. 3. We had better do specific-field research in cooperation between oriental medical colleges and Korea Institute of Oriental Medicine(KIOM) as well as study a target cancers such as hepatic cancer, pulmonary cancer and gastric cancer more intensively than all cancers domestically. 4. Our country must keep communication with China having many clinical data, Taiwan chiefly doing the combined tharapy between oriental and western medicines, Japan having done basic study actively on cancer.

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Stabilization Converter Design and Modeling of LEO Satellite Power Systems (저궤도 위성의 전력 시스템 안정화를 위한 모델링 및 제어)

  • Yun, Seok-Teak;Won, Young-Jin;Lee, Jin-Ho
    • Journal of Satellite, Information and Communications
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    • v.5 no.2
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    • pp.29-33
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    • 2010
  • Satellites industry has been developing with the commercial and military needs. Because power system of satellite is very important to survival operation and hard to test, increasing reliability is very critical. Due to LEO small satellites are very sensitive to power system, effective stabilization control is important. Therefore, this paper introduce methods for general modeling of power converting system which it can be used design of controller and analysis of external disturbance influences. In conclusion, a modeling of LEO small satellites power converting system and a possible guide line to design reliable controller which optimizing power converters of LEO small satellite are generated.

The use of culture systems for the study of oligodendrocyte development and injury: The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes

  • Park, Song-Kyu;Kim, Hwan-Mook;Vartanian, Timothy
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2002.05a
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    • pp.14-23
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    • 2002
  • Development of oligodendrocytes and the generation of myelin internodes within the spinal cord depends on regional signals derived from the notochord and axonally derived signals. Neuregulin (NRG)-1, localized in the floor plate as well as in motor and sensory neurons, is necessary for normal oligodendrocyte development. Oligodendrocytes respond to NRGs by activating members of the erbB receptor tyrosine kinase family. Here, we show that erbB2 is not necessary for the early stages of oligodendrocyte precursor development, but is essential for proligodendroblasts to differentiate into galactosylcerebroside-positive (GalC+) oligodendrocytes. In the presence of erbB2, oligodendrocyte development is normal. In the absence of erbB2 (erbB2-/-), however, oligodendrocyte development is halted at the proligodendroblast stage with a >10-fold reduction in the number of GalC+ oligodendrocytes. ErbB2 appears to function in the transition of proligodendroblast to oligodendrocyte by transducing a terminal differentiation signal, since there is no evidence of increased oligodendrocyte death in the absence of erbB2. Furthermore, known survival signals for oligodendrocytes increase oligodendrocyte numbers in the presence of erbB2, but fail to do so in the absence of erbB2. Of the erbB2-/- oligodendrocytes that do differentiate, all fail to ensheath neurites. These data suggest that erbB2 is required for the terminal differentiation of oligodendrocytes and for development of myelin.

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Functional Characteristics of C-terminal Lysine to Cysteine Mutant Form of CTLA-4Ig

  • Kim, Bongi;Shin, Jun-Seop;Park, Chung-Gyu
    • IMMUNE NETWORK
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    • v.13 no.1
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    • pp.16-24
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    • 2013
  • CTLA-4Ig is regarded as an inhibitory agent of the T cell proliferation via blocking the costimulatory signal which is essential for full T cell activation. To improve applicability, we developed the CTLA-4Ig-CTKC in which the c-terminal lysine had been replaced by cysteine through single amino acid change. The single amino acid mutation of c-terminus of CTLA-4Ig was performed by PCR and was checked by in vitro transcription and translation. DNA construct of mutant form was transfected to Chinese hamster ovary (CHO) cells by electroporation. The purified proteins were confirmed by Western blot and B7-1 binding assay for their binding ability. The suppressive capacity of CTLA-4Ig-CTKC was evaluated by the mixed lymphocyte reaction (MLR) and in the allogeneic pancreatic islet transplantation model. CTLA-4Ig-CTKC maintained binding ability to B7-1 molecule and effectively inhibits T cell proliferation in MLR. In the murine allogeneic pancreatic islet transplantation, short-term treatment of CTLA-4Ig-CTKC prolonged the graft survival over 100 days. CTLA-4Ig-CTKC effectively inhibits immune response both in MLR and in allogeneic islet transplantation model, indicating that single amino acid mutation does not affect the inhibitory function of CTLA-4Ig. CTLA-4Ig-CTKC can be used in vehicle-mediated drug delivery system such as liposome conjugation.

Feedback Semi-Definite Relaxation for near-Maximum Likelihood Detection in MIMO Systems (MIMO 시스템에서 최적 검출 기법을 위한 궤환 Semi-Definite Relaxation 검출기)

  • Park, Su-Bin;Lee, Dong-Jin;Byun, Youn-Shik
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.33 no.12C
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    • pp.1082-1087
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    • 2008
  • Maximum Likelihood (ML) detection is well known to exhibit better bit-error-rate (BER) than many other detectors for multiple-input multiple-output (MIMO) channel. However, ML detection has been shown a difficult problem due to its NP-hard problem. It means that there is no known algorithm which can find the optimal solution in polynomial-time. In this paper, Semi-Definite relaxation (SDR) is iteratively applied to ML detection problem. The probability distribution can be obtained by survival eigenvector out of the dominant eigenvalue term of the optimal solution. The probability distribution which is yielded by SDR is recurred to the received signal. Our approach can reach to nearly ML performance.