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Antitumor Activity of LB42907, a Potent and Selective Farnesyltransferase Inhibitor: Synergistic Effect in Combination with Other Anticancer Drugs

  • Park, Ji-Hyun;Koo, Sun-Young;Kim, Dong-Myung;Kim, Kwi-Hwa;Jeong, Shin-Wu;Chung, Hyun-Ho;Cho, Heung-Soo;Park, Joong-Hoon;Yim, Hyeon-Joo;Lee, Jin-Ho;Koh, Jong-Sung;Kim, Se-Mi
    • Bulletin of the Korean Chemical Society
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    • v.29 no.7
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    • pp.1303-1310
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    • 2008
  • Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

Isolation Method of Mushroom Infesting Pests from Mushroom-Growing Compost (버섯배지에서 버섯해충류 분리방법)

  • Lee, Heung-Su;Kim, Kyu-Jin;Song, Geun-Woo;Kim, Jin-Ho
    • The Korean Journal of Mycology
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    • v.27 no.4 s.91
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    • pp.289-292
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    • 1999
  • We investigated the isolation method of mushroom infesting pests, Lycoriella mali, Coboldia fuscipes, Histiostoma sp. from mushroom-growing compost. Sugar solution of different densities (0, 10, 20, 30, 40, 50%) was tested to provide a means of seperating mushroom pests from the compost media. Thus, 40% sugar solution was suitable for isolation. The sieve size to entrap the pests was $30{\sim}140$ mesh; Lycoriella mali was trappped mainly $30{\sim}65$ mesh sieve, Coboldia fuscipes was caught mainly $30{\sim}100$ mesh sieve, Histiostoma sp. was trapped mainly $65{\sim}140$ mesh sieve. An isolation procedure was as follows; The infested compost was disintegrated in water and poured onto a set of 16, 30, 80, 140-mesh sieve. The material caught in the sieve is added in 40% sugar solution and then most compost particle were massed at the bottom while the supernatant contains mushroom pests. The upperlayer material was poured into a Seperatory funnel and the sediment at the bottom is drained off. The remaining material are washed off examination dish for study.

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The effect of Bu-Zhong-Yi-Qi-Tang on ultraviolet B-induced skin damages in mouse (자외선 B 조사 마우스에서 피부손상에 대한 보중익기탕의 효과)

  • Kim, Joong-Sun;Lee, Hae-June;Song, Myoung-Sub;Seo, Heung-Sik;Moon, Changjong;Kim, Jong-Choon;Bae, Chun-Sik;Jo, Sung-Kee;Kim, Sung-Ho
    • Korean Journal of Veterinary Research
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    • v.49 no.1
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    • pp.17-22
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    • 2009
  • The effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) on the changes of ultraviolet (UV) light B radiation-induced apoptotic sunburn cell (SBC) and epidermal ATPase-positive dendritic cell (DC) in SKH1- hr or ICR mouse were investigated. The mice were treated with UVB (200 mJ/$cm^2$) and were sacrificed 24 h later. BZYQT (50 mg/kg of body weight) or vehicle (saline) was given i.p. at 36 and 12 h before irradiation, and 30 min after irradiation or BZYQT cream (0.2%) or cream base (vehicle) was topically treated at 24 h and 15 min before irradiation, and immediately after irradiation. The skin of SKH1-hr mouse prepared from the back of untreated mice exhibited about 0.3 SBC/cm length of epidermis, and 24 h after UV irradiation, the applied areas show an increased number of SBCs. But the frequency of UVB-induced SBC formation was reduced by intraperitoneal injection of BZYQT extract (p < 0.01). The numbers of DC in normal ICR mouse were 628.00 ${\pm}$ 51.56 or 663.20 ${\pm}$ 62.58 per $mm^2$ of ear epidermis. By 1 day after UVB treatment, the number of ATPase-positive cells/$mm^2$ were decreased by 39.0% or 27.1% in i.p. or topical application group with vehicle. Treatment of BZYQT was associated with increase of 33.9% in i.p. group (p < 0.05) or 2.7% in topical application group in the number of ATPase positive cells compared with the irradiation control group. The results presented herein that BZYQT administration could reduce the extent of skin damages produced by UVB.

Isolation and Identification of Secondary Metabolites from the Ovary of Nelumbo nucifera (연꽃 자방으로부터 이차대사물질 분리 및 구조동정)

  • Ji, Seung-Heon;Lee, Jae-Won;Lee, Seung-Eun;Lee, Young-Seob;Kim, Geum-Soog;Ahn, Young-Sup;Baek, Nam-In;Lee, Yi;Lim, Heung-Bin;Lee, Dae Young
    • Journal of Life Science
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    • v.26 no.10
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    • pp.1196-1201
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    • 2016
  • The ovary parts of Nelumbo nucifera were extracted in 80% methanol (MeOH), and the concentrated extract was then partitioned using n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH), and H2O, successively. Using an octadecyl silica gel (ODS) column, silica gel (SiO2) column chromatography, and a HPLC purification system, five compounds were isolated from the n-hexane fraction obtained from the extract of N. nucifera ovary. The chemical structures of the metabolites were determined using several spectroscopic methods, including NMR and GC/MS and MS of 1-eicosanol (1), cycloartenol (2), trans-squalene (3), pentadecanoic acid (4), and β-sitosterol (5). This study is a first attempt to isolate and identify secondary metabolites from the ovary of N. nucifera. The results indicated that the extract of N. nucifera ovary has biological effects, such as antibacterial and -tumor activity. Therefore, it could decrease the risk of HIV transmission through breastfeeding.

Diagnostic effectiveness of fine needle aspiration cytology on pediatric cervical lymphadenopathy (소아 경부 림프절 종대의 세침 흡인 세포검사의 진단적 유용성)

  • Byun, Jun Chul;Choe, Byung Kyu;Hwang, Jin-Bok;Kim, Heung Sik;Lee, Sang Sook
    • Clinical and Experimental Pediatrics
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    • v.49 no.2
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    • pp.162-166
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    • 2006
  • Purpose : There are few reports in Korean literature on the diagnostic efficacy of fine needle aspiration cytology(FNAC) for pediatric cervical lymphadenopathy. This study examined the diagnostic value of FNAC on cervical lymphadenopathy in children. Methods : Data from 57 pediatric patients(aged 0.3 to 14 years) who underwent FNAC due to cervical lymphadenopathy between January 2001 and March 2005 was reviewed retrospectively. Results : Reactive cervical lymphadenitis was the most common result of the FNAC(52.5 percent). Malignant disease were revealed in 14 percent of all cases. The sensitivity, specificity was 86 percent and 96 percent, respectively. The positive and negative predictive values for malignant disease was 75 percent and 98 percent, respectively. There were two false-positive cases on FNAC; one case of Langerhans cell histiocytosis, and another with infectious mononucleosis. A false-negative case on FNAC was found to be acute lymphocytic leukemia. In seven cases(12 percent), the final diagnosis was confirmed by an open biopsy after the FNAC. There were four FNAC cases where the specimen was not satisfactory for making a diagnosis(7 percent). There were no serious complications of the FNAC procedure. Conclusion : FNAC had a high diagnostic efficacy for evaluating children with cervical lymphadenopathy.

Effects of Angelica gigas Nakai diet on lipid metabolism, alcohol metabolism and liver function of rats administered with chronic ethanol (당귀의 첨가 식이가 흰쥐의 지방대사와 알콜대사 및 간기능에 미치는 영향)

  • Cha, Youn-Soo;Choi, Dong-Seong;Oh, Suk-Heung
    • Applied Biological Chemistry
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    • v.42 no.1
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    • pp.29-33
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    • 1999
  • To investigate the effects of Angelica gigas Nakai diet on lipid metabolism, alcohol metabolism and liver function of rats administered with chronic ethanol, Sprague-Dawley male rats were fed either AIN-76 diet (control), control diet with ethanol, control plus Angelica gigas Nakai diet, or control plus Angelica gigas Nakai diet with ethanol for 30 days. On the 21st day, all of the rats were given an oral dose of ethanol and blood-ethanol concentration was monitored for the next 5 hours. The results obtained were: 1) Upon ethanol administration, the blood ethanol concentration was decreased from 2 hr significantly in the group of control plus Angelica gigas Nakai diet compared with control diet group; 2) The blood ethanol oxidation rate was increased in the group of control plus Angelica gigas Nakai diet with ethanol compared with control diet group or control plus Angelica gigas Nakai diet group. After 30 days, rats were sacrificed and then lipid and enzyme determinations in blood and liver were carried out. The results obtained were: 1) LDL-cholesterol in the blood of control plus Angelica gigas Nakai diet group was decreased significantly compared with control diet group; 2) Angelica gigas Nakai diet decreased liver triglyceride and total lipid and blood ${\gamma}-GTP$ level increased due to the chronic ethanol administration. These data suggest that Angelica gigas Nakai can have a recovery function on the symptoms of alcohol related diseases.

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Control Efficacy of Bordeaux Mixture against Pepper Anthracnose (고추 탄저병에 대한 보르도액의 방제 효과)

  • Park, Se-Jung;Lee, Soo-Min;Gwon, Hyeon-Wook;Lee, Hotaek;Kim, Heung Tae
    • The Korean Journal of Pesticide Science
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    • v.18 no.3
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    • pp.168-174
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    • 2014
  • It was conducted to evaluate the control efficacy of Bordeaux mixture on pepper anthracnose in vitro and in vivo. The suppressive efficacy of Bordeaux mixture on mycelial growth and spore germination of Colletotrichum acutatum was investigated on PDA, cellophane membranes and pepper fruits, respectively. Furthermore, its control value was evaluated on detached pepper fruits inoculated with C. acutatum by wound and non-wound inoculation method, and in fields. The mycelial growth of C. acutatum JC24 was inhibited by 90.0% on PDA amended with $937{\mu}g\;mL^{-1}$ of Bordeaux mixture. While the spore germination of C. acutatum JC24 was inhibited perfectly on cellophane membranes treated at $187{\mu}g\;mL^{-1}$ of Bordeaux mixture, that on fruits inoculated with the pathogen by wound inoculation and non-wound inoculation method was inhibited by 88.1% and 91.3%, respectively. Although the control value on fruits treated with $937{\mu}g\;mL^{-1}$ of Bordeaux mixture was 17.6% in wound inoculation method, it was 58.8% in non-wound inoculation method. In fields, when Bordeaux mixture was sprayed five times at 14 day-intervals, it showed 55.7% and 61.7% of control value in 2012 and 2013, respectively. We think Bordeaux mixture was able to use as an eco-friendly organic farming material to control pepper anthracnose based on the above-mentioned results.

Monitoring for the Resistance of Strobilurin Fungicide Against Botrytis cinerea Causing Gray Mold Disease (Strobilurin계 살균제에 대한 잿빛곰팡이병균 Botrytis cinerea의 저항성 검정)

  • Kim, Ah Hyeong;Kim, Seon Bo;Han, Ki Don;Kim, Heung Tae
    • The Korean Journal of Pesticide Science
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    • v.18 no.3
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    • pp.161-167
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    • 2014
  • This study was conducted to investigate the resistance of Botrytis cinerea to azoxystrobin, which belongs to strobilurin fungicides. The sensitivity of B. cinerea isolates, which were collected from infected pepper, strawberry, cucumber and tomato by a single spore isolation, to the fungicide was tested through a agar dilution method on PDA amended with fungicides and $100{\mu}g\;mL^{-1}$ of salicylhydroxamic acid (SHAM). All isolates of B. cinerea tested in this study were classified as a sensitive and a resistant group by $1.0{\mu}g\;mL^{-1}$ of $EC_{50}$ value to azoxystrobin. While the sensitive isolates accounted for 46.5% of B. cinerea population, the resistant ones did for 53.5%. According to the regions isolating B. cinerea, the highest isolation frequency was showed as 81.1% in Chungnam among the all. Among 4 host plants as pepper, strawberry, cucumber and tomato, the highest isolation frequency was obtained in strawberry, while the lowest was done in pepper. The isolate resistant to azoxystrobin showed the cross resistance to other fungicides included into strobilurins as kresoxim-methyl and trifloxystrobin. In spite of an excellent efficacy of strobilurins, it should be taken care to use them in the field, because of the high risk in the fields.

Growth and Production of Macrobenthic Fauna on a Macrotidal Flat, Inchon, Korea -II. Production of the Razor Clam, Solen (Solen) strictus (Bivalvia, Solenidae) from Chokchon Tidal Flat- (인천연안 간석지산 주요 저서생물의 성장과 생물생산 -II. 척전지역 간석지에 서식하는 맛조개, Solen (Solen) strictus의 생물생산-)

  • HONG Jae-Sang;PARK Heung-Sik
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.27 no.5
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    • pp.560-571
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    • 1994
  • A single station representative of the razor clam, Solen (Solen) strictus, on a macrotidal flat, Inchon, Korea was sampled at bimonthly intervals between May 1989 and July 1990 by using a can corer. Estimates of growth rate and annual production of this razor clam have been made using the techniques of cohort growth analysis. Growth rate and production were highest during the first year after spawning and recruitment. The annual production was $2.83g\;DWt/m^2/yr$, mean annual biomass $256.3\;g/w^20$, and a turnover time of 5.00 yea, giving an annual turnover rate (P/B) of $0.20\;yr^{-1}$. The total annual production in wet weight ($33.22g\;WWt/m^2/yr$) appeared to consist of water in live flesh($72.6\%$) and shell($18.9\%$), whereas the dry weight of the soft parts was $8.52\%$, the ash-free dry weight $5.4\%$, and the ash content $3.1\%$ of the total wet weight.

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A STUDY ON PREVALENCE AND PATTERN OF DENTAL ANOMALIES (치아 이상의 발생 빈도와 양상에 관한 연구)

  • Jean, Seung-June;Lee, Jae-Ha;Chai, Hyung-Jun;Shan, Heung-Kyu
    • Journal of the korean academy of Pediatric Dentistry
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    • v.23 no.2
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    • pp.429-449
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    • 1996
  • An objective definition of the anomaly is not avaliable and most investigators define the term differently or fail to describe their criterion. Because dental anomaly may lead to many complications, early detection and diagnosis of dental anomalies are essential steps in the evaluation of the child patient and in treatment planning. These procedures require detailed medical and dental histories, through clinical examination and the use of radiographs. So, this study was designed to find out the prevalence of dental anomalies. The clinical and roentgenographic examination was undertaken for 8,054 children at age from 0 to 15 years and statistical analysis was done. The results were as follows : 1. Among the examined subjects, 2,134 subjects(26.5%) showed dental anomalies. The prevalence of individual dental anomalies were as follows : supernumerary teeth 15.6%, congenitally missing teeth 6.6%, fusion 2.2%, odontoma 0.35%, microdontia 1.2%, macrodontia 0.05%, gemination 0.22%, talon cusp 0.36%, dens evaginatus 0.24%, dens invaginatus 0.15%, dilaceration 0.27%, taurodontism 0.09%, abnormal tooth position 1.7%, natal & neonatal teeth 0.92%, amelogenesis imperfecta 0.01%. 2. Significant correlations between the groups with individual dental anomalies were as follows : between group I and other groups, there was negative correlation, especially group I and group II. And the correlation coefficient between male and female showed differences. 3. For the supernumerary teeth group, the prevalence of male was higher than female(p<0.001). While for the congenitally missing teeth, macrodontia, microdontia, abnormal tooth position group, the prevalence of female was greater than male(p<0.001). 4. For the congenitally missing teeth group, the mandibular primary lateral incisor showed the highest incidence in primary dentiton, while mandibular lateral incisor in permanent dentition. In the mandible(72.5%), this site showed higher prevalence than in maxilla. In the case with deciduous congenitally missing teeth, the prevalence of successive permanent congenitally missing teeth was about 33.9%, the incidence was highest in mandibular lateral incisors. 5. Most supernumerary teeth existed on middle area and showed inverted position and unerupted state. In addition, supernumerary teeth showed higher incidence on maxilla (99.3%). 6. In the case with deciduous fused teeth, the prevalence of successive permanent congenitally missing teeth was 39.9%, while that of successive permanent fused teeth was 2.7%. And the highest rate of the prevalence (40.3%) appeared in fusion of mandibular deciduous lateral incisor and canine. 7. In the case of odontoma, the prevalence was higher in maxilla(78.6%) and anterior region(82.7%) than mandible and posterior region.

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