• Title/Summary/Keyword: Resistance mechanisms

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Exploiting tumor cell senescence in anticancer therapy

  • Lee, Minyoung;Lee, Jae-Seon
    • BMB Reports
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    • v.47 no.2
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    • pp.51-59
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    • 2014
  • Cellular senescence is a physiological process of irreversible cell-cycle arrest that contributes to various physiological and pathological processes of aging. Whereas replicative senescence is associated with telomere attrition after repeated cell division, stress-induced premature senescence occurs in response to aberrant oncogenic signaling, oxidative stress, and DNA damage which is independent of telomere dysfunction. Recent evidence indicates that cellular senescence provides a barrier to tumorigenesis and is a determinant of the outcome of cancer treatment. However, the senescence-associated secretory phenotype, which contributes to multiple facets of senescent cancer cells, may influence both cancer-inhibitory and cancer-promoting mechanisms of neighboring cells. Conventional treatments, such as chemo- and radiotherapies, preferentially induce premature senescence instead of apoptosis in the appropriate cellular context. In addition, treatment-induced premature senescence could compensate for resistance to apoptosis via alternative signaling pathways. Therefore, we believe that an intensive effort to understand cancer cell senescence could facilitate the development of novel therapeutic strategies for improving the efficacy of anticancer therapies. This review summarizes the current understanding of molecular mechanisms, functions, and clinical applications of cellular senescence for anticancer therapy.

A Study of Localized Corrosion Mechanisms in the Multilayered Coatings by Cathodic Arc Deposition (음극아크증착법으로 합성한 다층박막의 국부부식 기구에 관한 연구)

  • 김호건;안승호;이정호;김정구;한전건
    • Journal of Surface Science and Engineering
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    • v.36 no.4
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    • pp.301-306
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    • 2003
  • Multilayered WC-Ti/suv $1-x/Al_{x}$ N coatings were deposited on AISI D2 steel using cathodic arc deposition (CAD) method. These coatings contain structural defects such as pores or droplets. Thus, the substrate is not completely isolated from the corrosive environment. The growth defects (pores, pinholes) in the coatings are detrimental to corrosion resistance of the coatings used in severe corrosion environments. The localized corrosion behavior of the coatings was studied in deaerated 3.5 wt.% NaCl solution using electrochemical techniques (potentiodynamic polarization test) and surface analyses (GDOES, SEM, AES, TEM). The porosity was calculated from the result of potentiodynamic polarization test of the uncoated and coated specimens. The calculated porosity is higher in the $WC-Ti_{0.6}$ $Al_{0.4}$ N than others, which is closely related to the packing factor. The positive effects of greater packing factor act on inhibiting the passage of the corrosive electrolyte to the substrate and lowering the localized corrosion kinetics. From the electrochemical tests and surface analyses, the major corrosion mechanisms can be classified into two basic categories: localized corrosion and galvanic corrosion.

Analysis of Rice Blast Infection and Resistance-inducing Mechanisms via Effectors Secreted from Magnaporthe oryzae

  • Saitoh, Hiromasa;H, Kanzaki;K, Fujisaki;R, Terauchi
    • 한국균학회소식:학술대회논문집
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    • 2015.05a
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    • pp.61-61
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    • 2015
  • Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most destructive diseases of rice worldwide. The rice - M. oryzae pathosystem has become a model in the study of plant - fungal interactions due to its economic importance and accumulating knowledge. During the evolutionary arms race with M. oryzae, rice plants evolved a repertoire of Resistance (R) genes to protect themselves from diseases in a gene-for-gene fashion. M. oryzae secretes a battery of small effector proteins to manipulate host functions for its successful infection, and some of them are recognized by host R proteins as avirulence effectors (AVR), which turns on strong immunity. Therefore, the analysis of interactions between AVRs and their cognate R proteins provide crucial insights into the molecular basis of plant - fungal interactions. Rice blast resistance genes Pik, Pia, Pii comprise pairs of protein-coding ORFs, Pik-1 and Pik-2, RGA4 and RGA5, Pii-1 and Pii-2, respectively. In all three cases, the paired genes are tightly linked and oriented to the opposite directions. In the AVR-Pik/Pik interaction, it has been unraveled that AVR-Pik binds to the N-terminal coiled-coil domain of Pik-1. RGA4 and RGA5 are necessary and sufficient to mediate Pia resistance and recognize the M. oryzae effectors AVR-Pia and AVR1-CO39. A domain at the C-terminus of RGA5 characterized by a heavy metal associated domain was identified as the AVR-binding domain of RGA5. Similarly, physical interactions among Pii-1, Pii-2 and AVR-Pii are being analyzed.

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Studies on the Selections, the Cross-Resistance and the Eserase Activity in the Strain of German Cockroack, Blattella germanica L.Selected with dichlorvos (바퀴에 대한 Dichlorvos(DDVP)의 누대도태, 교차저항성 및 효소활성에 관한 연구)

  • 이형래;김정화;방종렬;최관선
    • Korean journal of applied entomology
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    • v.33 no.2
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    • pp.74-80
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    • 1994
  • The german cockroach, Blattello germanica L, populations were successively selected with dlchlowos for 11 generations. The resulting selected shin was investigated the resistance development. the cross resistance and the esterase actim@. In the dichlowos-selected(Rd) strain, the values of LCs increased 858 times more compared to the susceptible (S) strain. In the dich!o~vos-selected (Rd) strains, the cross-res~stance to chlorpyrifos, propoxur, fenvalerate and pemethnn showed 3.35. 4.09. 283 and 2.00 times. Esterase.activity of the Rd strain showed 1.33 times higher than that of the S strain in the filter paper test. In comparison of zymogram paitems of the estemse isoryme by thin agarose gel electrophoresis against the german cockroach, the S strain was separated by 4 bands uf esterase 3, 5, 6 and 8 bands and the Rd strain was separated by 6 bands of esterase 1, 2, 4, 5, 7 and 8 bands, and the resistant mechanisms of the Rd strain were considered as the 4 bands of esterase-1.2.4 and 7 bands except the common 2 bands of esterase.6 and 8 bands.

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Screening Rice Cultivars for Resistance to Bacterial Leaf Blight

  • Fred, Agaba Kayihura;Kiswara, Gilang;Yi, Gihwan;Kim, Kyung-Min
    • Journal of Microbiology and Biotechnology
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    • v.26 no.5
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    • pp.938-945
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    • 2016
  • Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious threats to rice production. In this study, screening of rice for resistance to BLB was carried out at two different times and locations; that is, in a greenhouse during winter and in an open field during summer. The pathogenicity of Xoo race K1 was tested on 32 Korean rice cultivars. Inoculation was conducted at the maximum tillering stage, and the lesion length was measured after 14 days of inoculation. Five cultivars, Hanareum, Namcheon, Samgdeok, Samgang, and Yangjo, were found to be resistant in both the greenhouse and open-field screenings. Expression of the plant defense-related genes JAmyb, OsNPR1, OsPR1a, OsWRKY45, and OsPR10b was observed in resistant and susceptible cultivars by qRT-PCR. Among the five genes tested, only OsPR10b showed coherent expression with the phenotypes. Screening of resistance to Xoo in rice was more accurate when conducted in open fields in the summer cultivation period than in greenhouses in winter. The expression of plant defense-related genes after bacterial inoculation could give another perspective in elucidating defense mechanisms by using both resistant and susceptible individuals.

Observations of Infection Structures after Inoculation with Colletotrichum orbiculare on the Leaves of Cucumber Plants Pre-inoculated with Two Bacterial Strains Pseudomonas putida or Micrococcus luteus

  • Jeun, Yong-Chull;Lee, Kyung-Hoo
    • Mycobiology
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    • v.33 no.3
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    • pp.131-136
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    • 2005
  • Infection structures were observed at the penetration sites on the leaves of cucumber plants inoculated with Colletotrichum orbiculare using a fluorescence microscope. The cucumber plants were previously drenched with suspension of bacterial strains Pseudomonas putida or Micrococcus luteus. The plants pre-inoculated with both bacterial strains were resistant against anthracnose after inoculation with C. orbiculare. To investigate the resistance mechanism by both bacterial strains, the surface of infected leaves was observed at the different time after challenge inoculation. At 3 days after inoculation there were no differences in the germination and appressorium formation of conidia of C. orbiculare as well as in the callose formation of the plants between both bacteria pre-inoculated and non-treated. At 5 days, the germination and appressorium formation of the fungal conidia were, however, significantly decreased on the leaves of plants pre-inoculated with M. luteus at the concentration with $1.0{\times}10^7\;cfu/ml$. Furthermore, callose formation of plants cells at the penetration sites was apparently increased. In contrast, there were no defense reactions of the plants at the concentration with $1.0{\times}10^6\;cfu/ml$ of M. luteus. Similarly, inoculation P. putida caused no plant resistance at the low concentration, whereas increase of callose formation was observed at the higher concentration. The results of this study suggest that the resistant mechanisms might be differently expressed by the concentration of pre-treatment with bacterial suspension.

Investigation of Ru ohmic contacts to n-ZnO thin film for optoelectronis devices (광소자용 n-ZnO 박막의 Ru 오믹 접촉 연구)

  • 김한기;김경국;박성주;성태연;윤영수
    • Journal of the Korean Vacuum Society
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    • v.11 no.1
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    • pp.35-42
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    • 2002
  • We fabricate thermally stable and low resistance Ru ohmic contacts to $n-ZnO:Al(3\times10^{18}\textrm{cm}^{-3})$, grown by specially designed dual target sputtering system. It is shown that the as-deposited Ru contact produces a specific contact resistance of $2.1{\times}10^{-3}{\Omega}\textrm{cm}^2$. Annealing of the Ru contacts leads to the improvement of current-voltage characteristics. For example, annealing of the contact at $700^{\circ}C$ for 1 min produces a contact resistance of $3.2{\times}10^{-5}}{\Omega}\textrm{cm}^2$. furthermore, the metallisation scheme is found to be thermally stable: the surface of the contact is fairly smooth with a rms roughness of 1.4 nm upon annealing at $700^{\circ}C$. These results strongly indicate that the Ru contact represents a suitable metallisation scheme for fabrication of high-performance ZnO-based optical devices and high-temperature devices. In addition, possible mechanisms are suggested to describe the annealing temperature dependence of the specific contact resistance.

Changes in Esterase Activity and Acetylcholinesterase Sensitivity of Insecticide-selected Strains of the Brown Planthopper(Nilaparvata lugens Stal) (저항성 벼멸구의 효소활성 변화에 관한 연구)

  • 박형만;최승윤
    • Korean journal of applied entomology
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    • v.30 no.2
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    • pp.117-123
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    • 1991
  • Acetylcholinesterase(AChE) and esterase activities as mechanisms of resistance to fenobucarb, carbofuran and diazinon in the insecticide-selected brown planthopper strains were investigated. Although there was no significant difference in AChE activity from suscept tible and resistant strains, AChE insensitivity was highly increased in the carbam없e insecticide-selected strains. On the other hand, esterase activity was moderately increa잃d in all the s selected strains. It is concluded that the cross-resistance and the level of resistance in the b brown planthopper can be explained by the combination of altered AChE and high esterase a activity, although a possible involvement of other factor(s) can not be excluded.

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Comparative Proteomic Profiling of Pancreatic Ductal Adenocarcinoma Cell Lines

  • Kim, Yikwon;Han, Dohyun;Min, Hophil;Jin, Jonghwa;Yi, Eugene C.;Kim, Youngsoo
    • Molecules and Cells
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    • v.37 no.12
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    • pp.888-898
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    • 2014
  • Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.

Effects of Amomum cadamomum Linne Extract on TNF-α-induced Inflammation and Insulin Resistance in 3T3-L1 Adipocytes

  • Kang, Kyung-Hwa;Song, Choon-Ho
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.30 no.1
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    • pp.54-60
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    • 2016
  • Amomum cadamomum Linne (ACL) has long been utilized against the inhibited qi movement related diseases such as dyspepsia, acute gastroenteritis, vomiting and diarrhea in Korean medicine. We speculated that ACL could improve the metabolic disorders such as obesity and type 2 diabetes through removing the phlegm-dampness and promoting the qi movement or stagnation. This study was designed to investigate effects and molecular mechanisms of ACL extract on the improvement of adipocyte dysfunction induced by TNF-α in 3T3-L1 adipocytes. Potential roles of ACL extract in the lipogenesis, inhibition of inflammatory cytokines and insulin resistance, were investigated in this study. Also, we examined the adipose genes and signaling molecules related to insulin resistance and glucose uptake to elucidate its mechanism. Our data demonstrated that TNF-α significantly incresed the release of lipid droplets and the production of MCP-1 and IL-6 from adipocytes. In gene expression, TNF-α reduced the expression of aP2, PPARγ, C/EBPα, GLUT4, and IRS-1 related to lipogenesis and insulin sesitivity, while TNF-α increased the expression of MCP-1 related to inflammation. In addition, TNF-α down-regulated the PPARγ and IRS-1 protein and up-regulated the IRS-1 Ser307 phosphorylation. These alterations induced by TNF-α were prevented by the treatment of ACL extract. Thus, our results indicate that ACL extract can be used to prevent from the TNF-α-induced adipocyte dysfunction through insulin and PPARγ pathways.