• Title/Summary/Keyword: translational research

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Regulation of Tumor Neceosis Factor-${\alpha}$ Receptors and Signal Transduction Pathways

  • Han, Hyung-Mee
    • Toxicological Research
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    • v.8 no.2
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    • pp.343-357
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    • 1992
  • Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

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Evaluation of Setup Errors for Tomotherapy Using Differently Applied Vacuum Compression with the Bodyfix Immobilization System (토모테라피 치료 시 Bodyfix System에서 진공압박에 따른 환자 위치잡이오차(Setup errors)의 평가)

  • Jung, Jae-Hong;Cho, Kwang-Hwan;Lee, Jeong-Woo;Kim, Min-Joo;Lim, Kwang-Chae;Moon, Seong-Kwon;Kim, Yong-Ho;Suh, Tae-Suk
    • Progress in Medical Physics
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    • v.22 no.2
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    • pp.72-78
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    • 2011
  • The aim of this study is to evaluate the patient's setup errors in TomoTherapy (Hi-Art II, TomoTherapy, USA) Bodyfix system (Medical Intelligence, Ele-kta, Schwabmuchen, Germany) pressure in the vacuum compression, depending on and were evaluated. Bodyfix immobilization system and vacuum pressure was compression applied to the patients who received Tomotherapy thoracic and abdominal area, 21 patients were selected and TomoTehpay treatment total 477 of MVCT images were obtained. The translational (medial-lateral: ML, anterior-posterior: AP, superior-inferior: SI directions) and rolling were recorded and analyzed statistically. Using Pearson's product-moment coefficient and One-way ANOVA, the degree of correlation depending on the different vacuum pressure levels were statistically analyzed for setup errors from five groups (p<0.05). The largest average and standard deviation of systematic errors were 6.00, 5.95 mm in the AP and SI directions, respectively. The largest average of random errors were 4.72 mm in the SI directions. The correlation coefficients were 0.485, 0.244, and 0.637 for the ML-Roll, AP-Vector, and SI-Vector, respectively. SI-Vector direction showed the best relationship. In the results of the different degree of vacuum pressure in five groups (Pressure range: 30~70 mbar), the setup errors between the ML, SI in both directions and Roll p=0.00 (p<0.05) were shown significant differences. The average errors of SI direction in the vacuum pressure of 40 mbar and 70 mbar group were 4.78 mm and -0.74 mm, respectively. In this study, the correlation between the vacuum pressure and the setup-errors were statistically analyzed. The fact that setup-errors in SI direction is dependent in vacuum pressure considerly setup-errors and movement of interal organs was identified. Finally, setup-errors, and it, based on the movement of internal organs in Bodyfix system we should apply more than 50 mbar vacuum pressure. Based on the results of this study, it is suggested that accuracy of the vacuum pressure and the quantitative analysis of movement of internal organs and the tumor should be studied.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China

  • Li, Xing;Dong, Min;Wen, Jing-Yun;Wei, Li;Ma, Xiao-Kun;Xing, Yan-Fang;Deng, Yun;Chen, Zhan-Hong;Chen, Jie;Ruan, Dan-Yun;Lin, Ze-Xiao;Wang, Tian-Tian;Wu, Dong-Hao;Liu, Xu;Hu, Hai-Tao;Lin, Jia-Yu;Li, Zhuang-Hua;Liu, Yuan-Chao;Xia, Qing;Jia, Chang-Chang;Wu, Xiang-Yuan;Lin, Qu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6311-6316
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    • 2015
  • Background: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. Materials and Methods: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. Results: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision-making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. Conclusions: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.

The Anti-angiogenic Potential of a Phellodendron amurense Hot Water Extract in Vitro and ex Vivo (in Vitro와 ex vivo에서 황백 온수추출물의 신생혈관 억제효과)

  • Kim, Eok-Cheon;Kim, Seo Ho;Bae, Kiho;Kim, Han Sung;Gelinsky, Michael;Kim, Tack-Joong
    • Journal of Life Science
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    • v.25 no.6
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    • pp.693-702
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    • 2015
  • Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

Physiological Changes of Saccharomyces cerevisiae KNU5377 Occurred in the Process of the 48-hour Ethanol Fermentation at 40℃ (40℃ 48시간 에탄올발효 과정 중 일어나는 Saccharomyces cerevisiae KNU5377의 생리 변화)

  • Kwak, Sun-Hye;Kim, Il-Sup;Kang, Kyung-Hee;Lee, Jung-Sook;Jin, Ingn-Yol
    • Journal of Life Science
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    • v.21 no.1
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    • pp.146-154
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    • 2011
  • In this study, physiological changes in a thermotolerant yeast Saccharomyces cerevisiae KNU5377 cell exposed to 48-hour alcohol fermentation at $40^{\circ}C$ were investigated. After 12 hours of alcohol fermentation at $40^{\circ}C$, the $C_{16:1}$ unsaturated acid of plasma membrane increased to 1.5 times more than the $C_{16:0}$ saturated fatty acid, and to about 2 times more for the $C_{18:1}$ unsaturated fatty acid. Fermentation at both $30^{\circ}C$ and $37^{\circ}C$ fermentation showed the same pattern as that done at $40^{\circ}C$. The pH of the alcohol-fermentation medium was reduced to pH 4.1 from a starting pH of 6.0 through the 12-hr fermentation and then maintained this level during the continuing fermentation. With the process of fermentation, the remaining glucose was reduced, but its amount remaining during the $40^{\circ}C$-fermentation was less reduced than those fermented at $30^{\circ}C$ and $37^{\circ}C$. In the study investigating the changing pattern of cellular proteins in the alcohol-fermenting cells, the SDS-PAGE and 2-D data indicated the most expressed dot was phosphoglycerate kinase, which is one enzyme involved in glycolysis. Why this enzyme was most expressed in the cells exposed to unfavorable conditions such as high temperature, increasing concentration of produced alcohol and long time exposure to other stress factors remains unsolved.

Functional implications of gene expression analysis from rice tonoplast intrinsic proteins during seed germination and development (벼 종자에서 액포막 aquaporin (tonoplast intrinsic protein) 유전자의 발현과 기능)

  • Huh, Sun-Mi;Lee, In-Sook;Kim, Beom-Gi;Shin, Young-Seop;Lee, Gang-Seop;Kim, Dool-Yi;Byun, Myung-Ok;Kim, Dong-Hern;Yoon, In-Sun
    • Journal of Plant Biotechnology
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    • v.37 no.4
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    • pp.517-528
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    • 2010
  • Rice seed maturation and germination involve drastic changes in water and nutrient transport, in which tonoplast aquaporins may play an important role. In the present study, gene expression profiles of 10 tonoplast intrinsic proteins (TIP) from rice were investigated by RT-PCR during seed development and germination. OsTIP3;1 and OsTIP3;2 were specifically expressed in mature seeds. Their transcript level rapidly decreased after onset of seed germination and gene expression was induced by ABA treatment. In contrast, expression of OsTIP2;1 and OsTIP4;3 was not seed specific as transcripts were found in vegetative tissues as well. Their respective transcript levels decreased at an early stage of seed development, whereas they increased at a later stage of seed germination and elongation of embryonic roots and shoots. When seed germination was inhibited by various stress conditions and ABA, expression of OsTIP2;1 and OsTIP4;3 was completely suppressed. In contrast, the expression level of OsTIP2;2 rapidly increased after seed imbibition and the transcript level was maintained under conditions inhibiting seed germination. These results implicate that tissue specific and developmental transcriptional regulation of OsTIPs in rice seeds depends on their specific function. In addition, OsTIPs can be discriminated by different potential phosphorylation and methylation sites in their protein structures. OsTIP3;1 and OsTIP3;2 possess unique phosphorylation signatures at their N-terminal domain, loop B and loop E, respectively. OsTIP2;1 and OsTIP4;3 have a potential methylation site at their Nterminal domain. This suggests that activity of specific tonoplast aquaporins may be regulated by post-translational modification as well as by transcriptional control.

Report on the Eradication of Nutria (Myocastor coypus Molina, 1782), an Invasive Alien Species, from Jeju-do, South Korea - Case of Songdang-ri, Jeju-si - (제주도 침입외래생물 Nutria (Mycastor coypus Molina, 1782)의 퇴치 사례 보고 - 제주시 송당지역의 사례 -)

  • Ga-Ram Kim;Jun-Won Lee;Seon-Mi Park;Sung-Hwan Choi;Young-Hun Jung;Hong-Shik Oh
    • Korean Journal of Environment and Ecology
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    • v.36 no.6
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    • pp.582-591
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    • 2022
  • This study was conducted to eliminate Myocastor coypusMolina, 1782 (Nutria) from Jeju Special Self-Governing Province, South Korea. Habitat identification and eradication were carried out from September to November 2013, and a survey was carried out until June 2022 to check whether the eradication was successful. The habitat was identified with unmanned cameras, interviews, and literature surveys, and the capture was performed using the trapping method with food to attract nutria to the habitat area. The study area for the follow-up survey, which was set relatively wide considering nutria's home range, included wetlands and rivers within 4.0 km2 of the habitat area (eradication area). As a result, nutria's habitat was confirmed only at Songdang Ranch, Songdang-ri, of Jeju Island, with traces of habitat (footprints, excrement, and burrows) confirmed in waterways and ponds within the pasture. Eight individuals were captured, including four females, three males, and one individual in too advanced a state of decay to identify the sex. The follow-up survey thoroughly investigated the habitat and its surroundings, focusing on three areas with permanent water, Seongeup Reservoir, Cheonmi Creek, and Molsuni Pond, but no signs of habitat were identified. Therefore, it is determined that nutria inhabiting Jeju Island has been completely eradicated. It is believed that the successful eradication of nutria in the Jeju Special Autonomous Region was possible due to a synergy between 1) the eradication of nutria at the beginning of the settlement phase through rapid capture after confirming the nutria habitat and 2) the delayed expansion period because of rare presence of wetlands, where water is constantly stagnant, on Jeju Island. These results imply that quickly identifying the ecological characteristics of the species and preventing disturbances before they or at the beginning of the ecological disturbance through control and eradication at the initial stage of settlement before the expansion stage is an effective measure to cope with the influx of alien species.