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Study on the Safety of Bojungbangdocktang Ethanol Extract (보정방독탕 에탄올 추출물의 안전성에 대한 연구)

  • Lee, Eun-Ok;Lee, Hyo-Jeong;Lee, Hyo-Jung;Jeong, Soo-Jin;Choi, Do Young;Jung, Hee-Jae;Ahn, Kyoo-Seok;Kang, Jong-Gu;Kim, Sung-Hoon
    • Journal of Korean Traditional Oncology
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    • v.15 no.1
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    • pp.37-45
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    • 2010
  • Bojungbangdocktang (BJBDT), a formula of eight Oriental herbs, is a modified herbal prescription of Bangdoktang and Bojungbangamtang. Recently, BJBDT was demonstrated to inhibit angiogenesis induced by vascular endothelial growth factor in human umbilical vein endothelial cells, enhance hematopoiesis and protect cisplatin-induced cytotoxicity in normal MCF-10A breast cells. Nevertheless, there is no safety study of BJBDT before clinical trial so far. Thus, in the current study, we investigated the toxicity about ethanol-extracted BJBDT. Male and female Spraque Dawley (SD) rats were given orally by BJBDT at 250, 500, and 1000 mg/kg for 4 weeks. Mortality, clinical signs and measured change of body weight, food consumption and water consumption were observed. In addition, we performed ophthalmologic, urinary, hematological, blood serum biochemical and histopathological examination. Any general toxicity was not found in BJBDT treated group. Also, there were no significant differences in the parameters such as body weight, food consumption and water consumption, a lot of urine and blood factor levels except HCT, MCHC, Ca, TG, Glucose and T-Bilirubin level compared with control group. Although HCT was elevated and TG was decreased in male rats, and MCHC, Glucose and T-Bilirubin were elevated and Ca and HCT were decreased in female rats, these were within normal ranges. Finally, we determined that maximum tolerated dose (MTD) was 1000 mg/kg and no observed adverse effect level (NOAEL) was 500 mg/kg. Taken together, these results demonstrated that BJBDT is very safe to SD rats.

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The Evaluation of Space Dose Distribution for Digital Mammography Equipment (디지털 유방촬영장비에 관한 공간선량율 평가)

  • Jung, Hongmoon;Jung, Jaeeun;Hyun, Hyejin;Won, Doyeon
    • Journal of the Korean Society of Radiology
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    • v.9 no.1
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    • pp.61-65
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    • 2015
  • Mammography equipment is an essential detector for making an early diagnosis of female's breast lesion. Recently, in most hospitals, a digital mammography detector is used due to the wide and consistent supply of digital mammography equipment. However, the average effective radiation is increasing due to the indiscreet use of CR or DR mammography. The purpose of this study is to recognize the possible indirect radiation damage, which can be occurred due to an excessive effective exposure of radiation, by evaluating spacial radiation rate of the digital mammography detector used for female patient. Consequently, the high mount of spacial radiation showed digital mammography equipment on the horizontal direction. Considering the result, digital mammography equipment should be installed by avoiding along the horizontal direction.

Establishment of a Stable Cell Line Expressing Green Fluorescence Protein-fused Hypoxia Inducible Factor-1α for Assessment of Carcinogenicity of Chemical Toxicants

  • Kim, Sung-Hye;Seo, Hee-Won;Lee, Min-Ho;Chung, Jin-Ho;Lee, Byung-Hoon;Lee, Mi-Ock
    • Toxicological Research
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    • v.25 no.4
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    • pp.189-193
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    • 2009
  • Hypoxia inducible factor $1\alpha$ (HIF-$1\alpha$) is a potential marker of carcicnogenesis since it is overexpresssed in many human cancers such as brain, breast, and uterus, and its role has implicated in tumor cell growth and metastasis. In this study, we established a stable cell line that express green fluorescence protein (GFP)-fused hypoxia inducible factor $1\alpha$ (HIF-$1\alpha$) and evaluated the potential use of this cell line for assessment of carcinogenicity of chemical toxicants. Western blot analysis as well as fluorescence measurements showed that protein-level of GFP-HIF-$1\alpha$ was significantly enhanced in a dose-dependent manner upon treatment of hypoxia mimicking agents such as dexferrioxamine and $CoCl_2$. Well-Known tumor promoters such as mitomycin and methyl methanesulfonate. significantly induced the fluorescence intensity of GFP-HIF-$1\alpha$, whereas the known negative controls such as o-anthranilic acid and benzethonium chloride, did not. These results indicate that HIF-$1\alpha$ could be a biological parameter for detection of tumor initiators/promoters and suggest that the GFP-HIF-$1\alpha$ cell line is a useful system for screening of carcinogenic toxicants.

An Innate Bactericidal Oleic Acid Effective Against Skin Infection of Methicillin-Resistant Staphylococcus aureus: A Therapy Concordant with Evolutionary Medicine

  • Chen, Chao-Hsuan;Wang, Yanhan;Nakatsuji, Teruaki;Liu, Yu-Tsueng;Zouboulis, Christos C.;Gallo, Richard L.;Zhang, Liangfang;Hsieh, Ming-Fa;Huang, Chun-Ming
    • Journal of Microbiology and Biotechnology
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    • v.21 no.4
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    • pp.391-399
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    • 2011
  • Free fatty acids (FFAs) are known to have bacteriocidal activity and are important components of the innate immune system. Many FFAs are naturally present in human and animal skin, breast milk, and in the bloodstream. Here, the therapeutic potential of FFAs against methicillin-resistant Staphylococcus aureus (MRSA) is demonstrated in cultures and in mice. Among a series of FFAs, only oleic acid (OA) (C18:1, cis-9) can effectively eliminate Staphylococcus aureus (S. aureus) through cell wall disruption. Lauric acid (LA, C12:0) and palmitic acid (PA, C16:0) do not have this ability. OA can inhibit growth of a number of Gram-positive bacteria, including hospital and community-associated MRSA at a dose that did not show any toxicity to human sebocytes. The bacteriocidal activities of FFAs were also demonstrated in vivo through injection of OA into mouse skin lesions previously infected with a strain of MRSA. In conclusion, our results suggest a promising therapeutic approach against MRSA through boosting the bacteriocidal activities of native FFAs, which may have been co-evolved during the interactions between microbes and their hosts.

Biological Effectiveness of Methionine Hydroxy-analogue Calcium Salt in Relation to DL-Methionine in Broiler Chickens

  • Elwert, C.;de Fernandes, E. Abreu;Lemme, A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.10
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    • pp.1506-1515
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    • 2008
  • Two feeding trials were conducted to assess the relative bioavailability (RBV) of methionine hydroxy analogue calcium salt (MHA-Ca) in comparison to DL-methionine (DL-Met). Male Ross 308 (1-38 days) and Cobb 500 chickens (1-42 days) were used in studies 1 and 2, respectively. Experimental diets based on wheat and soybean meal or sorghum and soybean meal were fed during three phases. In both experiments graded levels of DL-Met and MHA-Ca were supplemented to Met+Cys deficient basal diets. Additionally, in experiment 1, increasing levels of a DL-Met preparation diluted with corn starch to 65% purity (DL-Met65) were supplemented. Birds were kept in floor pens and feed and water were available ad libitum. Body weights and feed consumption were recorded at the beginning and end of the experimental periods and weight gain and feed efficacy were computed subsequently. At the end of the experiments, a number of birds were slaughtered for carcass evaluation (dressing percentage, breast meat yield). Dose response data were analysed by both ANOVA and nonlinear common plateau asymptotic regression. In both experiments birds responded significantly to increasing levels of either methionine source. However, RBV of MHA-Ca compared to DL-Met was markedly (in many cases significantly) below 84%, the value which would have been expected from MHA-Ca's chemical characteristics. Excluding some extremely low RBV figures of trial 2, RBV of MHA-Ca averaged to about 63% in relation to DL-Met. In addition, supplementation of DL-Met65 allowed confirmation of nonlinear common plateau asymptotic regression to be suitable to determine RBV.

Apoptosis Induction in MV4-11 and K562 Human Leukemic Cells by Pereskia sacharosa (Cactaceae) Leaf Crude Extract

  • Asmaa, Mat Jusoh Siti;Al-Jamal, Hamid Ali Nagi;Ang, Cheng Yong;Asan, Jamaruddin Mat;Seeni, Azman;Johan, Muhammad Farid
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.475-481
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    • 2014
  • Background: Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia. Materials and Methods: Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. $IC_{50}$ concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting. Results: P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells. Conclusions: These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.

Gamma Knife Radiosurgery for Ten or More Brain Metastases

  • Kim, Chang-Hyun;Im, Yong-Seok;Nam, Do-Hyun;Park, Kwan;Kim, Jong-Hyun;Lee, Jung-Il
    • Journal of Korean Neurosurgical Society
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    • v.44 no.6
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    • pp.358-363
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    • 2008
  • Objective : This study was performed to assess the efficacy of GKS in patients with ten or more brain metastases. Methods : From Aug 2002 to Dec 2007, twenty-six patients (13 men and 13 women) with ten or more cerebral metastatic lesions underwent GKS. The mean age was 55 years (32-80). All patients had Karnofsky performance status (KPS) score of 70 or better. According to recursive partitioning analysis (RPA) classification, 3 patients belonged to class I and 23 to class II. The location of primary tumor was lung (21), breast (3) and unknown (2). The mean number of the lesions per patient was 16.6 (10-37). The mean cumulated volume was 10.9 cc (1.0-42.2). The median marginal dose was 15 Gy (9-23). Overall survival and the prognostic factors for the survival were retrospectively analyzed by using Kaplan Meier method and univariate analysis. Results : Overall median survival from GKS was 34 weeks (8-199). Local control was possible for 79.5% of the lesions and control of all the lesions was possible in at least 14 patients (53.8%) until 6 months after GKS. New lesions appeared in 7 (26.9%) patients during the same period. At the last follow-up, 18 patients died; 6 (33.3%) from systemic causes, 10 (55.6%) from neurological causes, and 2 (11.1 %) from unknown causes. Synchronous onset in non-small cell lung cancer (p=0.007), high KPS score (${\geq}80$, p=0.029), and controlled primary disease (p=0.020) were favorable prognostic factors in univariate analysis. Conclusion : In carefully selected patients, GKS may be a treatment option for ten or more brain metastases.

Therapeutic Effect of Gamma Knife Radiosurgery for Multiple Brain Metastases

  • Lee, Chul-Kyu;Lee, Sang-Ryul;Cho, Jin-Mo;Yang, Kyung-Ah;Kim, Se-Hyuk
    • Journal of Korean Neurosurgical Society
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    • v.50 no.3
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    • pp.179-184
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    • 2011
  • Objective : The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods : We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results : The overall median survival after GKRS was $9.1{\pm}1.7$ months. Among various factors, primary tumor control was a significant prognostic factor ($11.1{\pm}$1.3 months vs. $3.3{\pm}2.4$ months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion : According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase.

Which One is More Effective, Filgrastim or Lenograstim, During Febrile Neutropenia Attack in Hospitalized Patients with Solid Tumors?

  • Sonmez, Ozlem Uysal;Guclu, Ertugrul;Uyeturk, Ummugul;Esbah, Onur;Turker, Ibrahim;Bal, Oznur;Budakoglu, Burcin;Arslan, Ulku Yalcintas;Karabay, Oguz;Oksuzoglu, Berna
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1185-1189
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    • 2015
  • Background: Chemotherapy-induced febrile neutropenia (FN) with solid tumors causes mortality and morbidity at a significant rate. The purpose of this study was to compare the effects of filgastrim and lenograstim started with the first dose of antibiotics in hospitalized patients diagnosed with FN. Materials and Methods: Between February 2009 and May 2012, 151 patients diagnosed with FN were evaluated, retrospectively. In those considered appropriate for hospitalization, convenient antibiotic therapy with granulocyte colony stimulating factors was started within first 30 minutes by completing necessary examinations in accordance with FEN guide recommendations. Results: In this study, 175 febrile neutropenia attacks in 151 patients were examined. Seventy three of the patients were male and 78 were female. The average age was 53.6 and 53.6, respectively. The most common solid tumor was breast carcinoma in 38 (25%). One hundred and five FN patients (58%) were those who received granulocyte colony stimulating factors as primary prophylaxis. Conclusions: While studies comparing both drugs generally involve treatments started for prophylaxis, this study compared the treatment given during the febrile neutropenia attack. Compared to lenograstim, filgastrim shortens the duration of hospitalization during febrile neutropenia attack by facilitating faster recovery with solid tumors.

Evaluation of polyherbal formulation and synthetic choline chloride on choline deficiency model in broilers: implications on zootechnical parameters, serum biochemistry and liver histopathology

  • Selvam, Ramasamy;Saravanakumar, Marimuthu;Suresh, Subramaniyam;Chandrasekeran, CV;Prashanth, D'Souza
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.11
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    • pp.1795-1806
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    • 2018
  • Objective: The study was designed to establish choline deficiency model (CDM) in broilers for evaluating efficacy of polyherbal formulation (PHF) in comparison with synthetic choline chloride (SCC). Methods: A total of 2,550 one-day-old Cobb 430 broiler chicks were randomly assigned to different groups in three experiments. In experiment 1, G1 and G2 served as normal controls and were fed a basal diet with 100% soybean meal (SBM) as a major protein source supplemented with and without SCC, respectively. In G3, G4, G5, and G6 groups, SBM was replaced at 25%, 50%, 75%, and 100% by soy protein isolate (SPI) to induce a graded level of choline deficiency. In experiment 2, PHF (500 and 1,000 g/ton) in comparison with SCC (1,000 g/ton) were evaluated. In experiment 3, dose-response of PHF (200, 400, and 500 g/ton) with SCC (400 g/ton) was determined. Results: Replacement of SBM by SPI produced a linear decrease in body weight gain (BWG) with a poor feed conversion ratio (FCR). 25% SBM replacement by SPI yielded an optimum negative impact on BWG and FCR; hence, it is considered for further studies. In experiment 2, PHF (500 and 1,000 g/ton) and SCC (1,000 g/ton) showed a similar performance in BWG, FCR and relative liver weight. In experiment 3, PHF produced an optimum efficacy at 400 g/ton and was comparable to SCC in the restoration of serum aspartate aminotransferase activity, abdominal fat, breast muscle lipid content and liver histopathological abnormalities. Conclusion: Replacement of SBM by SPI caused choline deficiency characterised by worsening of BWG, FCR, elevation in liver enzymes and histopathological changes indicating fatty liver. CDM was found valid for evaluating SCC and PHF. It is concluded that PHF has the potential to mimic biological activities of SCC through the restoration of negative effects caused by CDM.