• Title/Summary/Keyword: leukemia cells

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Identification of a New 5'-Noncoding Exon Region and Promoter Activity in Human N-Acetylglucosaminyltransferase III Gene

  • Kang, Bong-Seok;Kim, Yeon-Jeong;Shim, Jae-Kyoung;Song, Eun-Young;Park, Young-Guk;Lee, Young-Choon;Nam, Kyung-Soo;Kim, June-Ki;Lee, Tae-Kyun;Chung, Tae-Wha;Kim, Cheorl-Ho
    • BMB Reports
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    • v.31 no.6
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    • pp.578-584
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    • 1998
  • In a previous paper (Kim et al., 1996a), the immediate 5' -flanking region and coding region of the human UDP-N -acetylglucosamine:-D-mannoside-1,4-Nacetylglucosaminyltransferase III (N-acetylglucosaminyitransferase- III; GnT-III) gene was reported, isolated and analyzed. Herein, we report on amplification of a new 5' -noncoding region of the GnT-III mRNA by single-strand ligation to single-stranded cDNA-PCR (5' -RACE PCR) using poly(A)+ RNA isolated from human fetal liver cells. A cDNA clone was obtained with 5' sequences (96 bp) that diverged seven nucleotides upstream from the ATG (+1) start codon. A concensus splice junction sequence, TCTCCCGCAG, was found immediately 5' to the position where the sequences of the cDNA diverged. The result suggested the presence of an intron in the 5' -noncoding region and that the cDNA was an incompletely reversetranscribed cDNA product derived from an mRNA containing a new noncoding exon. When mRNA expression of GnT-III in various human tissues and cancer cell lines was examined, Northern blot analysis indicated high expression levels of GnT-III in human fetal kidney and brain tissues, as well as for a number of leukemia and lymphoma cancer cell lines. Promoter activities of the 5' -flanking regions of exon 1 and the new noncoding region were measured in a human hepatoma cell line, HepG2, by luciferase assays. The 5'-flanking region of exon 1 was the most active, whilst that of exon 2 was inactive.

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Generation of Transgenic Chickens that Produce Bioactive Human Thrombopoietin (재조합 hTPO를 생산하는 형질전환 닭의 개발)

  • Kwon, Mo-Sun;Koo, Bon-Chul;Roh, Ji-Yeol;Lee, Hyun-A;Kim, Te-Oan
    • Reproductive and Developmental Biology
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    • v.32 no.3
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    • pp.159-166
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    • 2008
  • We report here the generation of transgenic chickens that produce human Thrombopoietin (hTPO) using replication-defective Moloney murine leukemia virus (MoMLV)-based vectors packaged with vesicular stomatitis virus G glycoprotein (VSV-G). For the retrovirus vectors, we used hCMV (human Cytomegalovirus) internal promoter to drive the hTPO gene. After confirming the expression of the hTPO gene in various target cells, the concentrated solution of recombinant retrovirus was injected beneath the blastoderm of non-incubated chicken embryos (stage X). The biological activity of the recombinant hTPO in target cell was significantly higher than its commercially available counterpart. Out of 132 injected eggs, 11 chicks hatched after 21 days of incubation and 4 hatched chicks were found to express vector-encoded hTPO gene. However, 3 out of the 4 transgenics died within one month of hatching. The major significance of this study is that it is one of the very few successful reports on the production of transgenic chickens as bioreactors aiming mass production of commercially valuable and biological active human cytokine proteins.

The Study of Dosimetry according to the Thickness of Beam Spoiler on Total Body Irradiation (전신방사선치료시 산란체의 두께에 따른 선량측정)

  • Kim, Youngjae;Jeon, Byeongkyou;Lee, Jaesik;Jung, Jaeeun
    • Journal of the Korean Society of Radiology
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    • v.8 no.5
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    • pp.265-269
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    • 2014
  • The therapy of total body irradiation on leukemia carries out to kill harmful bacteria or suppression of immune system by external beam therapy, which is a preparatory stage to reconstitute bone marrow before a pre-treatment of bone marrow transplantation to patients with health bone marrow cells. In case of this kind of radiation therapy, the spoiler use to increase surface dose of patient which varies depending on distance and thickness between patient and spoiler. In this study, the change was investigated the surface dose according to thickness of spoiler. The 0.5% increase of surface dose was observed with each 2.0 cm when the spioler in acrylic was prepared from 0.5 cm to 3.0 cm at intervals of 0.5 cm was evaluated. Based on this result, it suggests that this kind of application will be somewhat limited on clinical trials directly but proper surface dose can be useful method when is applied on patients of treatment prognosis who are required each different surface dose.

Anti-Inflammatory Activity of Three Kinds of Salvia and Its Active Compounds (3종의 배암차즈기에 대한 염증억제 활성 비교 및 활성성분 구명)

  • Shin, Han Jae;Gwak, Hyo Min;Jang, Mi;Park, Si Hwan;Min, Hye Jeong;Lee, Jeong Min;Lee, Moon Yong;Kim, Jong Han;Kim, Sung Won;Han, Chang Kyun;Kim, Seung Hyung
    • Korean Journal of Medicinal Crop Science
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    • v.24 no.5
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    • pp.401-407
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    • 2016
  • Background: Salvia has been widely cultivated for use in flavoring and folk medicines in many countries, including Korea and China. In this study, we investigated the anti-inflammatory activity and the underlying active compounds of Salvia extract and its fractions. Methods and Results: The anti-inflammatory activity was measured by assessing the inhibition of cysteinyl leukotriene production in rat basophilic leukemia (RBL)-2H3 mast cells. Salvia plebeia R. Br. was found to have the most potent inhibitory activity on leukotriene production than S. japonica and S. chanroenica had. Fifty percent ethanol extracts of S. plebeia R. Br. were successively partitioned with n-hexane, methylene chloride, ethyl acetate, 1-butanol and water. The ethyl acetate (EtOAc) fraction showed stronger anti-inflammatory activity than other solvent fractions did. The EtOAc fraction was subjected to silica gel column chromatography elution with a chloroform and methanol gradient system (100 : 1 ${\rightarrow}$ 1 : 1) yielding 10 fractions. Three kinds of fractions (chloroform:methanol = 20 : 1, 10 : 1 and 5 : 1) showed high inhibitory activity on leukotriene production. We confirmed the major compounds with anti-inflammatory activity from S. plebeia R. Br. Conclusions: In this study, the major components of S. plebeia that showed leukotriene production inhibitory activity were isolated using solvent extraction and silica gel column chromatography. Rosmarinic acid, hispidulin and luteolin were identified as the major compounds with anti-inflammatory effect.

Anti-inflammatory Action of Phenolic Compounds from Gastrodia elata Root

  • Lee, Ji-Yun;Jang, Young-Woon;Kang, Hyo-Sook;Moon, Hee;Sim, Sang-Soo;Kim, Chang-Jong
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.849-858
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    • 2006
  • Previous screening of the pharmacological action of Gastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The antiinflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4'-hydroxybenzyloxy)benzyl-methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried out in vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determined in vitro. These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.

Regulation of LIF Gene Expression by Interleukin-1 in the Mouse Peri-implantation Embryos and Uterine Endometrial Cells (생쥐의 착상시기 배아와 자궁내막세포에서 IL-1에 의한 LIF 유전자 발현 조절)

  • Lee, Jung-Bok;Kim, Joung-Woul;Oh, Eun-Jeong;Yang, Hye-Young;Ryu, Hyoung-Eun;Lee, Ji-Youn;Gye, Myung-Chan;Yoon, Hyun-Soo;Kim, Moon-Kyoo
    • Clinical and Experimental Reproductive Medicine
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    • v.27 no.2
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    • pp.183-190
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    • 2000
  • 연구목적: 포유류의 착상은 배아가 모체의 자궁벽에 매몰되는 현상으로 부착과 침투 과정을 거쳐 진행되며, 이 과정은 스테로이드 호르몬, 성장인자, 세포점착분자, 그리고 cytokine 등의 상호작용으로 이루어진다. 이 시기에 Interleukin-1 (IL-1)과 leukemia inhibitory factor (LIF) 등이 발현되는 것으로 알려져 있다. 본 실험에서는 이들의 발현이 착상과정에 어떠한 역할을 하는지 그 상관관계를 알아보고자 하였다. 재료 및 방법: 착상 전후의 배아와 자궁내막세포에서 LIF 유전자의 발현양상과 $IL-1{\beta}$와 IL-1 receptor antagonist (IL-1ra)를 처리한 LIF 유전자의 발현양상을 역전사중합효소연쇄반응 (RT-PCR)을 통해 비교하였다. 결과: 배아에서의 LIF 유전자 발현은 in vivo와 in vitro 모두에서 상실기와 포배기에 발현되었고, 자궁내막에서는 임신 1일과 4일째에 발현되었는데, 상실기보다는 포배기에, 그리고 임신 1일보다는 착상시기인 4일째의 자궁내막세포에서 발현양이 많은 것으로 나타났다. 자궁내막세포를 배양한 경우 LIF 유전자는 in vivo에서의 발현양상과 동일하게 임신 1일과 4일에 발현되었으며, 배양액에 $IL-1{\beta}$(500pgml)를 처리하였을 경우 LIF 유전자가 초기 임신 (1~5일) 중 발현되는 것으로 나타났다. 2-세포기 배아의 배양시에 $IL-1{\beta}$를 처리한 경우 8-세포기부터 LIF 유전자가 발현되었으며, 또한 IL-1ea(60 ng/ml)를 배양액에 첨가하였을 경우에는 임신1일째 자궁내막에서는 LIF 유전자가 발현되지 않은 반면, 임신 4일째의 자궁내막세포와 상실기, 포배기 배아 모두에서 LIF 유전자 발현이 감소하는 경향을 보였다. 결론: 이러한 결과는 착상 전후 배아와 자궁내막세포에서 IL-1에 의해 LIF 유전자 발현이 조절되며, 그 결과 착상에 영향을 줄 수 있다는 것을 의미한다. 또한 배아와 자궁내막세포에서 IL-1이 LIF 유전자 발현에 영향을 주는 것으로 보아 착상을 위해 IL-1과 LIF의 상호작용이 중요한 요인이라는 것을 확인할 수 있었다.

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Antitumor Activity of 7-[2-(N-Isopropylamino)ethyl]-(20s)-camptothecin, CKD602, as a Potent DNA Topoisomerase I Inhibitor

  • Lee, Jun-Hee;Lee, Ju-Mong;Kim, Joon-Kyum;Ahn, Soon-Kil;Lee, Sang-Joon;Kim, Mie-Young;Jew, Sang-Sup;Park, Jae-Gab;Hong, Chung-Il
    • Archives of Pharmacal Research
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    • v.21 no.5
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    • pp.581-590
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    • 1998
  • We developed a novel water-soluble camptothecin analobue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respecitively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to imduce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/$ED-{58}$) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in <5% tumor bearing mouse. this schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.

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MULTIPLE MYELOMA IN THE MANDIBLE MANIFESTED AS ORAL LESION OF PLASMACYTOMA: A CASE REPORT (악골에서 발견된 multiple myeloma의 구강내 plasmacytoma 병소: 증례보고)

  • Lee, Jeong-A;Park, Ji-Young;Yun, Sung-Hun;Park, Min-Kyu;Kim, Chang-Hyun;Park, Je-Uk
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.29 no.1
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    • pp.85-90
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    • 2007
  • Plasma cell neoplasms are generally categorized into four groups; multiple myeloma(MM), solitary plasmacytoma of the bone(SPB), plasma cell leukemias, and extramedullary plasmacytomas(EMP). These tumors may be further described as localized or diffuse in presentation. Localized plasma cell neoplasms are rare occurrences and include solitary plasmacytomas of the skeletal system, which account for 2-5% of all plasma cell neoplasms and extramedullary plasmacytomas of the soft tissue, which account for approximately 3% of all such neoplasms. A plasmacytoma is defined as any discrete, most likely solitary mass of neoplastic plasma cells either in the bone marrow or in various soft tissue sites. Diffuse lesions include the other two groups, multiple myeloma and plasma cell leukemia. The relationship between these processes has not yet been definitively characterized, but there appears to be a continuum in which both SPB and EMP often progress to MM. The patient was referred who had continuous deep throbbing bone pain and swelling on the left posterior gingival area of the mandible after extraction of the first and second molar. The result of intraoperative excisional biopsy of the lesion was confirmed as a plasmacytoma. And it revealed systemic multiple myeloma through the further diagnostic work-up. It is worth to report because of a rare case of multiple myeloma found in oral cavity as a form of plasmacytoma.

Studies on Antitumor Components of Collybia confluens (밀버섯의 항암성분에 관한 연구)

  • Kim, Sook-Hee;Kim, Jin-Sook;Jin, Mi-Rim;Kim, Ha-Won;Choi, Eung-Chil;Kim, Byong-Kak
    • Korean Journal of Pharmacognosy
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    • v.24 no.4
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    • pp.267-281
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    • 1993
  • To find antitumor components from higher fungi, the mycelia of Collybia confluens (Pers. ex Fr.) Kummer were cultured in artificial media. For efficient production of the mycelia, the influences of various modifications of culture conditions were examined. A water-soluble protein-bound polysaccharide fraction, Fr. A, was obtained from the mycelia by hot water extraction. When Fr. A was purified and fractionated by DEAE-cellulose and Sepbadex G-200 gel filtration chromatographies into four fractions which were designated B, C, C-I and C-II. The tumor inhibition ratios of these fractions ranged from 46% to 75% against the solid forms of sarcoma 180 in ICR mice at doses of 20 and 50 mg/kg/day when given intraperitoneally. Especially, Fr. C which was named Collyban(CB) exhibited a marked life-prolonging effect of the mice against ascitic forms of sarcoma 180 at a dose of 50 mg via i.p. administration. To extend spectra of the antitumor activities and eliminate the effects of allograft rejection, the characterization of antitumor effects of CB was performed in syngeneic host-tumor systems. It did not show any antitumor activity against L1210 murine leukemia in $CD_2Fl$ mice but prolonged their life span against ascitic forms of $MM_{46}$ carcinoma in $C_3H/He$ mice. Also it exhibited antitumor activity against human cervical cancer HeLa cells that were xenografted into nude mice having BALB/c genetic backgrounds by the i.p. injection at a dose of 100 mg/kg/day. In order to characterize the antitumor components, CB was examined by chemical analysis. It was acidic protein-bound polysaccharides composed of 31% polysaccharide, 27% protein and 3% hexosamine. CB was fractionated into two fractions, Fr. C-I(M.W.: 500 Kd) and Fr. C-II(M.W.:30 and 8 Kd) by Sephadex G-200 gel filtration chromatography.

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Assessment of In vitro Antioxidant, Antidiabetic and Cytotoxic Activities of Sphaeranthus africanus Extracts

  • Tran Thi Huyen;Julien Dujardin;Nguyen Thi Thu Huong;Chung Thi My Duyen;Nguyen Hoang Minh;Ha Quang Thanh;Dao Tran Mong;Ly Hai Trieu;Nguyen Mai Truc Tien;Mai Thanh Chung;Nguyen Nhat Minh;Nguyen Thi Ngoc Dan;Huynh Loi
    • Natural Product Sciences
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    • v.29 no.2
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    • pp.98-103
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    • 2023
  • Sphaeranthus africanus is commonly used as a traditional remedy for sore throats and pain treatment in Vietnam. The aerial parts have been studied for its anti-inflammatory and anti-proliferative properties. However, the antioxidant and antidiabetic potential of the plant has not been explored. In this work, hydrophilic extracts of the plant's aerial parts were prepared in order to investigate its antioxidant and anti-diabetic properties. Also, the cytotoxicity of the root was evaluated and compared to that of the aerial parts. All of the extracts inhibited lipid peroxidation with IC50 values ranging from 2.05 to 3.56 ㎍/mL, indicating substantial antioxidant activity. At an IC50 value of 4.80 ㎍/mL, the 50% ethanol extract exhibited the most potent inhibition of α-glucosidase. The cytotoxic activity of root extracts is 2 to 5-fold less than that of the aerial parts. Nevertheless, dichloromethane and ethyl acetate extracts of the root demonstrated a selective effect on leukemia cells, with no harm towards the normal HEK-293 cell line. This work provides a scientific support for the antioxidant and antidiabetic activity of the plant. Hence, it may find a promising material for the development of novel antioxidant and antidiabetic agents. More research can be conducted on the phytochemistry and anticancer activities of the plant's root.