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Synthesis, Antitumor Activity and Release Rate of Polymers Containing Anionic Group and 5-Fluorouracil

  • Kang, Nam-In;Lee, Sun-Mi;Ha, Chang-Sik;Cho, Won-Jei
    • Macromolecular Research
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    • v.9 no.5
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    • pp.277-284
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    • 2001
  • Poly(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride)s [poly(ETA)s] and poly($\alpha$-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil)s [poly(EETFU)s ] with various average molecular weights were prepared by photopolymerizations. The number average molecular weights of the fractionated poly(ETA)s and poly(EETFU)s determined by GPC were in the range of 3,600∼21,000 and 3,600-33,400, respectively. The release rate of 5-FU from poly(EETFU) decreased with increasing average molecular weight. The in vitro cytotoxicity of poly(ETA) against a normal cell line was lower than that of 5-fluorouracil(5-FU), The in vivo antitumor activities of the synthesized samples at dosage of 0.8 mg/kg against mice bearing sarcoma 180 tumor cell line decreased in the following order: poly(EETFU) > poly(ETA) > EETFU > ETA > 5-FU. The antiangiogenic activities of the poly(ETA)s were better than those of 5-FU.

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Studies on medicinal protection with KH-19 against side effect of 5-fIurouracil and its mechanism (KH-19의 5-flurouracil 부작용 억제 효력 및 기전 연구)

  • Yang, Dong-Sik;Sung, Hyun-Jea;Yoon, Yoo-Sik
    • Korean Journal of Oriental Medicine
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    • v.9 no.1
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    • pp.137-144
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    • 2003
  • The objective on this study was to investigate medicinal protection with KH-19, which was composed of 9 kinds of oriental herbs tonifying the blood, against side effect of chemotherapy in mice and its mechanism through microarray. Not only WBC (white blood cell), and PLT (platelet) as a hematopoiesis toxicity indicator but also spleen weight as an immune toxicity indicator was reduced significantly 7 day after. 5-flurouracil (FU) treatment. However, reduction of WBC, PLT, and spleen weight after 5-FU treatment was significantly recovered by KH-19. For mechanic study on KH-19 action, gene expression in mouse spleen treated 5-FU was compared with gene expression in mouse treated 5-FU and KH-19. The result indicates that 23 genes were increased. in expression level over 2 fold and 41 genes were decreased in expression level more than 2 fold at mouse spleen by KH-19 treatment. KH-19 mechanism may be complicated more than other drug which of mechanism were composed of single compound because KH-19 was composed of various compounds.

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CD4O Activation Protects Dendritic Cells from Anticancer Drug-Induced Apoptosis

  • Jun, Jae-Yeon;Joo, Hong-Gu
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.5
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    • pp.255-259
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    • 2003
  • Dendritic cells (DCs) play a critical role in various immune responses involving $CD4^+$ T cells and have been used to generate anti-tumor immunity. Chemotherapy induces severe side effects including immunosuppression in patients with cancer. Although immunosuppression has been studied, the effects of anticancer drugs on DCs are not fully determined. In this study, we demonstrated that CD40 activation strongly protected DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. DCspecific surface markers, including CD11c and major histocompatibility complex (MHC) class II, were used for identifying DCs. CD 40 activation with anti-CD40 mAb significantly enhanced the viability of DCs treated with 5-FU or mitomycin C, assayed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Fluorescence staining and analysis clearly confirmed the enhancing effect of anti-CD40 mAb on the viability of DCs, suggesting that CD40 activation may transduce critical signals for the viability of DCs. Annexin V staining assay showed that CD40 significantly protected DCs from 5-FU or mitomycin C-induced apoptosis. Taken together, this study shows that CD40 activation with anti-CD40 mAb has strong anti-apoptosis effect on DCs, suggesting that CD40 activation may overcome the immunosuppression, especially downregulation of number and function of DCs in chemotherapy-treated cancer patients.

Synthesis and Antitumor Activity of $N^1$-derivatives of 5-Fluorouracil (5-Fluorouracil 유도체 합성 및 항암작용)

  • 이희주;신혜순;진현숙;김지현;김종국
    • YAKHAK HOEJI
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    • v.37 no.1
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    • pp.89-94
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    • 1993
  • In order to find out a proper connecting bridge between 5-fluorouracil(5-FU) and a macromolecule such as a polypeptide, potentially hydrolytic N$^{1}$-derivartives of 5-FU have been systhesized and evaluated for their biological activity. When tested with in vitro leukemic L$_{1210}$ cells all the obtained derivartives exhibited slightly higher antitumor activity than the parent 5FU. Among them the N$^{1}$ -carbamoyl analogue 2 and N$^{1}$-acetamido analogue 6b showed 50% inhibition of the L$_{1210}$ cell growth at the concentrations of 5.01$\times$10$^{-8}$M and 1.03$\times$10$^{-7}$M, respectively. When tested against sarcoma 180 tumor cells inoculated into mice, the compounds 2 and 6b exhibited, respectively, 62% and 54% inhibition of the solid tumor growth at the 5-time doses of 100 mg/kg/day. Both compounds, N$^{1}$-carbamoyl analogue 2 and N$^{1}$-acetamido analogue 6b, realeased the parent 5-FU when incubated in the L$_{1210}$ cell cultural media for 5 hrs.

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Comparison of 29 Diagrams of Lung Originated from Ming Tang Zang Fu Tu (明堂臟腑圖) (명당장부도(明堂臟腑圖)에서 기원한 폐장도(肺臟圖) 29종의 비교)

  • Jo, Hak-Jun
    • The Journal of Korean Medical History
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    • v.29 no.1
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    • pp.11-31
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    • 2016
  • Objectives : The goal of this paper is to research what affected diagrams of lung originated from Ming Tang Zang Fu Tu during the time they were changed in. Methods : Diagrams of lung in Traditional Chinese and Japanese medical books had been collected as many as possible. Besides being grouped by Huang Longxiang (黃龍祥)'s classification, they were analysed by 4 form factors, e.g. shape, number, veins and petiole of leafs. Results : Reliability of this methods had been checked on by the correspondence with Huang's 14 standard books, before 29 diagrams of lung were selected from 33 books including 13 books that Huang had already made his proposal. The lobes in most of diagrams resembled 6 lanceolate or long oval leafs, or a maple leaf with 5 indentations. In most of diagrams, veins of leafs were described variously, more or less than 9 nodes often drew in petioles. Conclusions : Suwen (素問), Nan Jing (難經) and Wang Bing would had steadily worked on 29 diagrams of lung, since diagram of lung stemmed from Ming Tang Zang Fu Tu, went out into the world in Zhen Jiu Ju Ying (鍼灸聚英). But they were not drawn through dissection during same periods.

Evapotranspiration Estimation Study Based on Coupled Water-energy Balance Theory in River Basin

  • Xue, Lijun;Kim, JooCheol;Li, Hongyan;Jung, Kwansue
    • Proceedings of the Korea Water Resources Association Conference
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    • 2018.05a
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    • pp.146-146
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    • 2018
  • Basin evapotranspiration is the result of water balance and energy balance, which is affected by climate and underlying surface characteristics, the process is complex, and spatial and temporal variability is large, the evapotranspiration estimation of river basin is an important but difficult problem in the field of hydrology, over the years, many scholars devoted to the basin actual evapotranspiration estimation and achieved excellent results. We discuss Budyko coupled water-energy balance theory and evaporation paradox, then use the Fu's equation to estimate actual evapotranspiration yearly in different areas with different dryness. The result shows that Fu's equation has high precision for estimating evapotranspiration yearly in our selected study area, and the estimation result has higher precision in the area with high dryness. Then, we propose an improved formula which can be used to estimate actual evapotranspiration monthly. Furthermore, we found that the parameter in the formula reflects general conditions of underlying surface and it is affected by several factors, at last, we tried to propose the calculation formula. The study indicates that Fu's equation provides a reliable method for evapotranspiration estimation in dry regions as well as semi-humid and semi-arid regions, which has great significance for forecasting river basin water resources and inquiring into ecological water requirement.

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The MicroRNA-551a/MEF2C Axis Regulates the Survival and Sphere Formation of Cancer Cells in Response to 5-Fluorouracil

  • Kang, Hoin;Kim, Chongtae;Ji, Eunbyul;Ahn, Sojin;Jung, Myeongwoo;Hong, Youlim;Kim, WooK;Lee, Eun Kyung
    • Molecules and Cells
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    • v.42 no.2
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    • pp.175-182
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    • 2019
  • microRNAs regulate a diverse spectrum of cancer biology, including tumorigenesis, metastasis, stemness, and drug resistance. To investigate miRNA-mediated regulation of drug resistance, we characterized the resistant cell lines to 5-fluorouracil by inducing stable expression of miRNAs using lenti-miRNA library. Here, we demonstrate miR-551a as a novel factor regulating cell survival after 5-FU treatment. miR-551a-expressing cells (Hep3B-lenti-miR-551a) were resistant to 5-FU-induced cell death, and after 5-FU treatment, and showed significant increases in cell viability, cell survival, and sphere formation. It was further shown that myocyte-specific factor 2C is the direct target of miR-551a. Our results suggest that miR-551a plays a novel function in regulating 5-FU-induced cell death, and targeting miR-551a might be helpful to sensitize cells to anti-cancer drugs.

Do Islamic Stock Markets Diversify the Financial Uncertainty Risk? Evidence from Selected Islamic Countries

  • AZIZ, Tariq;MARWAT, Jahanzeb;ZEESHAN, Asma;PARACHA, Yaser;AL-HADDAD, Lara
    • The Journal of Asian Finance, Economics and Business
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    • v.8 no.3
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    • pp.31-38
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    • 2021
  • The study investigates the diversification behavior of Islamic stocks against US financial uncertainty. Considering limitations found in the literature, a comprehensive index of financial uncertainty (FU) is used, developed by Jurado, Ludvigson, and Ng (2015). The empirical analysis uses monthly data from four Islamic markets - Saudi Arabia, Malaysia, Indonesia, and Turkey - for the period from January 2010 to September 2019. Results of the bivariate EGARCH models show that Islamic stocks can be used for diversification purpose against the financial uncertainty of the US because the volatility of US uncertainty does not propagate in the Islamic stock markets. Moreover, findings show that the spillover effect of financial uncertainty varies with the FU forecast horizon. The spillover effect of FU increases with an increase in the FU forecast horizon and becomes significant over 3-month and 12-month periods in the case of Saudi Arabia. The current volatility of Islamic stock returns is independent of the size of shocks in past volatility. The leverage effect and asymmetry have been found in Saudi Arabia and Malaysia. The findings validate the arguments of the literature that Islamic markets are resilient facing uncertainties and perform well during crisis periods. The findings are important for investors in making better portfolio decisions.

Histone Deacetylases and their Inhibitors as Potential Therapeutic Drugs for cholangiocarcinoma - Cell Line findings

  • Sriraksa, Ruethairat;Limpaiboon, Temduang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2503-2508
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    • 2013
  • Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5 -fluorouacil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. $IC_{50}$ and $IC_{20}$ were then analyzed for each agent and cell line. Moreover, synergistic potentional of VPA or SAHA in combination with 5-FU at sub toxic does ($IC_{20}$) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less senstitive to classical chemotheraoeutic 5-FU was highly was sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU signiicantly inhibited cell proliferation in CCA cell lines compared to single sgent treatment($P{\leq}0.01$), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA.

Retrospective Evaluation of Heptaplatin Toxicities in Patients with Advanced Gastric Cancer (말기 암환자에 투여한 Heptaplatin의 신독성에 대한 후향적 평가)

  • Park, Mi-Sook;Kang, Min-Hee;Lim, Sung-Cil;Choi, Soon-Ok;Lee, Byung-Koo;Lee, Myung-Koo
    • Korean Journal of Clinical Pharmacy
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    • v.16 no.2
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    • pp.131-138
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    • 2006
  • Heptaplatin, a new platinum derivative, has several contradicting reports on the nephrotoxicity. Therefore, the aim of this study is to compare the toxicities of heptaplatin-containing regimens in the chemotherapy. This study was performed retrospectively on seventy-seven patients with advanced gastric cancer who did not receive chemotherapy within the last 1 months before taking of heptaplatin- or cisplatin-containing chemotherapy. The 38 patients among total patients was received heptaplatin-containing regimens (26 with SEF regimens: heptaplatin/epirubicin/5-FU, 12 with SF regimens: heptaplatin/5-FU) and the rest 39 patients was received cisplatin-containg regimens (11 with CEF regimens: cisplatin/epirubicin/5-FU, 28 with ELF regimens: epirubicin/leucovorin/5-FU). Before and after the chemotherapy serum creatinine (Scr) and proteinuria were measured by urine stick test in all patient groups. Also Scr was measured a day before the second cycle and did not vary significantly between groups. However Scr on cycle 3 were significantly higher in SEF and SF groups. In case of proteinuria, it was more frequent on cycle 1 in heptaplatin/5-FU group. Proteinuria before and after on cycle 2 was not different between the two cisplatin -containing groups, but was more frequent in heptaplatin-containing groups. The reason why the Scr measured was not so different could be because we excluded the patients who received only one cycle of heptaplatin and changed the regimen due to signs of nephrotoxcity. As the results nephrotoxicity such as protienuria was appeared to be more frequent with heptaplatin-treated patients. It suggests that the clinical consequences of the toxicity need to further evaluation and also the modalities to prevent or minimize nephrotoxicity of heptaplatin should be studied for future utilization of the drug.

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