• Title/Summary/Keyword: MRP-1

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The Use of MR Perfusion Imaging in the Evaluation of Tumor Progression in Gliomas

  • Snelling, Brian;Shah, Ashish H.;Buttrick, Simon;Benveniste, Ronald
    • Journal of Korean Neurosurgical Society
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    • v.60 no.1
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    • pp.15-20
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    • 2017
  • Objective : Diagnosing tumor progression and pseudoprogression remains challenging for many clinicians. Accurate recognition of these findings remains paramount given necessity of prompt treatment. However, no consensus has been reached on the optimal technique to discriminate tumor progression. We sought to investigate the role of magnetic resonance perfusion (MRP) to evaluate tumor progression in glioma patients. Methods : An institutional retrospective review of glioma patients undergoing MRP with concurrent clinical follow up visit was performed. MRP was evaluated in its ability to predict tumor progression, defined clinically or radiographically, at concurrent clinical visit and at follow up visit. The data was then analyzed based on glioma grade and subtype. Resusts : A total of 337 scans and associated clinical visits were reviewed from 64 patients. Sensitivity, specificity, positive and negative predictive value were reported for each tumor subtype and grade. The sensitivity and specificity for high-grade glioma were 60.8% and 87.8% respectively, compared to low-grade glioma which were 85.7% and 89.0% respectively. The value of MRP to assess future tumor progression within 90 days was 46.9% (sensitivity) and 85.0% (specificity). Conclusion : Based on our retrospective review, we concluded that adjunct imaging modalities such as MRP are necessary to help diagnose clinical disease progression. However, there is no clear role for stand-alone surveillance MRP imaging in glioma patients especially to predict future tumor progression. It is best used as an adjunctive measure in patients in whom progression is suspected either clinically or radiographically.

Simple Signal Reconstruction by Faster Adaptive MRP Algorithm (고속 적응 MRP 알고리즘에 의한 저주파 신호 복원)

  • Jeong, Won-Yong;Kim, Jong-Su;Choe, Tae-Won;Bae, Jin-Ho
    • The Journal of the Acoustical Society of Korea
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    • v.11 no.2
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    • pp.5-14
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    • 1992
  • In the fields of astronomy, communication, X-ray crystallography, and engineering, it is a very important and useful fact that the original signal can be reconstructed from a partial information, only spectral magnitude or phase, of the signal. In this paper, we proposed a modified iterative algorithm to solve the Magnitude Retrieval Problem (MRP) for 1-D, 2-D signals. In oder to accelerate the convergence rate, the unit constant initial function which is used in the references is replaced by the exponential initial function for the modified adaptive iterative method. As a result, MRP with 1-D signal and low-pass detail image is significantly enhanced from an iterative convergence rate and a computer storage memory points of view.

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Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

  • Tao, Fulin;Zhou, Yuanyuan;Wang, Mengwen;Wang, Chongyang;Zhu, Wentao;Han, Zhili;Sun, Nianxia;Wang, Dianlei
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.95-111
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    • 2022
  • Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

Correlation of Exercise-Induced Bronchoconstriction to $PC_{20}$ and Maximal Airway Narrowing on the Dose-Response Curve to Methacholine (운동유발성 기관지수축의 정도와 Methacholine 유발시험의 민감도 및 최대기도협착과의 관련성)

  • Lim, Hyung-Suk;Yoon, Kyung-Ae;Koh, Young-Yull
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.2
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    • pp.165-174
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    • 1995
  • Background: Exercise is one of the most common precipitants of acute asthma encountered in clinical practice. The development of airflow limitation that occurs several minutes after vigorous exercise, i. g. exercise-induced bronchoconstriction(EIB), has been shown to be closely correlated with the nonspecific bronchial hyperresponsiveness, which is the hallmark of bronchial asthma. All previous reports that assessed the correlation of EIB to nonspecific bronchial hyperresponsiveness have focused on airway sensitivity($PC_{20}$) to inhaled bronchoconstrictor such as methacholine or histamine. However, maximal airway narrowing(MAN), reflecting the extent to which the airways can narrow, when being exposed to high dose of inhaled stimuli, has not been studied in relation to the degree of EIB. Methods: Fifty-six children with mild asthma(41 boys and 15 girls), aged 6 to 15 years(mean${\pm}$SD, $9.9{\pm}2.5$ years) completed this study. Subjects attended the laboratory on two consecutive days. Each subject performed the high-dose methacholine inhalation test at 4 p.m. on the first day. The dose-response curves were characterized by their position($PC_{20}$) and MAN, which was defined as maximal response plateau(MRP: when two or three data points of the highest concentrations fell within a 5% response range) or the last of the data points(when a plateau could not be measured). On the next day, exercise challenge, free running outdoors for ten minutes, was performed at 9 a.m.. $FEV_1$ was measured at graduated intervals, 3 to 10 minutes apart, until 60 minutes after exercise. Response(the maximal ${\triangle}FEV_1$ from the pre-exercise value) was classified arbitrarily into three groups; no response((-) EIB: ${\triangle}FEV_1$<10%), equivocal response ($({\pm})$EIB:10%<${\triangle}FEV_1$<20%) and definite response($({\pm})$EIB:${\triangle}FEV_1$>20%). Results: 1) When geometric mean $PC_{20}$ of the three groups were compared, $PC_{20}$ of (+) EIB group was significantly lower than that of (-)EIB group. 2) There was a close correlation between $PC_{20}$ and the severity of EIB in the whole group(r=-0.568, p<0.01). 3) Of the total 56 subjects, MRP could be measured in 36 subjects, and the MRP of these subjects correlated fairly with the severity of EIB(r=0.355, p<0.05) 4) The MAN of (+) EIB group was significantly higher than that of (-)EIB group(p<0.01). 5) The MAN correlated well with the severity of EIB in the whole group(r=0.546, p<0.01). Conclusion: The degree of MAN as well as bronchial sensitivity($PC_{20}$) to methacholine is correlated well with the severity of EIB. The results suggest that the two main components of airway hyperresponsiveness may be equally important determinants of exercise reactivity, although the mechanism may be different from each other. The present study also provides further evidence that EIB is a manifestation of the increased airway reactivity characteristic of bronchial asthma.

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Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

  • Roy, Madhumita;Mukherjee, Sutapa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1403-1410
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    • 2014
  • Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone $SiHa^R$ (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and $SiHa^R$, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in $SiHa^R$ due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.

ATM Traffic Modeling with Markov Renewal Process and Performance Analysis (마코프 재생과정을 이용한 ATM 트랙픽 모델링 및 성능분석)

  • Jeong, Seok-Yun;Hur, Sun
    • Journal of the Korean Operations Research and Management Science Society
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    • v.24 no.3
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    • pp.83-91
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    • 1999
  • In order to build and manage an ATM network effectively under several types of control methods, it is necessary to estimate the performance of the equipments in various viewpoints, especially of ATM multiplexer. As for the method to model the input stream into the ATM multiplexer, many researches have been done to characterize it by, such as, fluid flow, MMPP(Markov Modulated Poisson Process), or MMDP (Markov Modulated Deterministic Process). We introduce an MRP(Markov Renewal Process) to model the input stream which has proper structure to represent the burst traffic with high correlation. In this paper, we build a model for aggregated heterogeneous ON-OFF sources of ATM traffic by MRP. We make discrete time MR/D/1/B queueing system, whose input process is the superposed MRP and present a performance analysis by finding CLP(Cell Loss Probability). A simulation is done to validate our algorithm.

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Comparative Uptake of Tc-99m Sestamibi and Tc-99m Tetrofosmin in Cancer Cells and Tissue Expressing P-Glycoprotein or Multidrug Resistance Associated Protein (P-Glycoprotein과 Multidrug Resistance Associated Protein을 발현하는 암세포와 종양에서 Tc-99m Sestamibi와 Tc-99m Tetrofosmin의 섭취율 비교)

  • Cho, Jung-Ah;Lee, Jae-Tae;Yoo, Jung-Ah;Seo, Ji-Hyoung;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Sohn, Sang-Gyun;Ha, Jeoung-Hee;Lee, Kyu-Bo
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.1
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    • pp.34-43
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    • 2005
  • Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

Comparison of the Uptakes of Tc-99m MIBI and Tc-99m Tetrofosmin in A549, an MRP-expressing Cancer Cell, In Vitro and In Vivo (MRP발현 인체 비소세포 폐암 A549에서 Tc-99m MIBI와 Tc-99m Tetrofosmin섭취의 비교)

  • Yoo, Jeong-Ah;Jeong, Shin-Young;Seo, Myung-Rang;Bae, Jin-Ho;Ahn, Byeong-Cheol;Lee, Kyu-Bo;Choi, Sang-Woon;Lee, Byung-Ho;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.6
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    • pp.382-392
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    • 2003
  • Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.