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HiF-1α siRNA and Cisplatin in Combination SuppressTumor Growth in a Nude Mice Model of Esophageal Squamous Cell Carcinoma

  • Liao, Hong-Ying;Wang, Gui-Ping;Gu, Li-Jia;Huang, Shao-Hong;Chen, Xiu-Ling;Li, Yun;Cai, Song-Wang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.473-477
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    • 2012
  • Introduction: The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-$1{\alpha}$ siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. Materials and Methods: Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-$1{\alpha}$ siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-$1{\alpha}$ mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. Results: In our nude mice model, HIF-$1{\alpha}$ siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-$1{\alpha}$ mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-$1{\alpha}$ siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF-$1{\alpha}$ siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-$1{\alpha}$ siRNA-treated groups (P<0.05). Conclusions: Down-regulated HIF-$1{\alpha}$ expression induced by siRNA could effectively suppress the growth of transplanted ESCC $in$ $vivo$. HIF-$1{\alpha}$ siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.

The Effect of a Video Exercise Program on Cancer-related Fatigue, Physical Function and Emotional Status in Patients with Cancer during Chemotherapy (동영상 운동프로그램이 항암 화학요법을 받는 암환자의 피로와 신체기능 및 정서상태에 미치는 효과)

  • Cho, Mee Young;Park, Ji Young;Lee, Chung Eun;Song, Su Kyung;Lee, Sun Hi;Byun, Eun Sung;Kim, Ji Youn;Park, Ok Sun;Kim, Soon Ho;Kang, Young Lynn;Han, Soo Young;Lee, Hyang Kyu;Choi, Hye Jin
    • Journal of Korean Clinical Nursing Research
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    • v.18 no.3
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    • pp.368-380
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    • 2012
  • Purpose: The purpose of this study was to evaluate the effects of a home-based video exercise program on cancer-related fatigue, physiological and psychological status in patients with colon and rectal cancers undergoing chemotherapy. Methods: The study design was a non-equivalent control group non-synchronized design. Data were collected from patients with colo-rectal cancers in Yonsei cancer center from July 5th to October 31st in 2011. There were 40 participants; 20 in the experimental group and 20 in the control group. The structured questionnaire was used to measure fatigue, physical function and emotional status. Data were analyzed using SPSS 18.0 and a chi-squre test, Fisher's exact test, Mann-Whitney U test and Wilcoxon signed- rank test were conducted to examine the homogeneity and the research hypotheses. Results: There was a statistically significant difference in White Blood Cell count in the experimental group compared with that of the control group. The exercise group showed a slight decrease of White Blood Cell count compared with that of the control group after 4 week program (z=-2.935, p=.003). However, there were no significant differences in fatigue, physiological and psychological status between the two groups. Conclusion: In this study, the developed video exercise program was effective in markedly slightly decreasing White Blood Cell count in patients with colo-rectal cancers undergoing chemotherapy. Therefore, utilizing the video exercise program can be an useful method to promote health among patients with cancer in clinical practice.

Assessment of DNA Viability in Long term-Stored Buffy Coat Species for the Korean Multicenter Cancer Cohort (한국인 다기관 암 코호트 시료의 DNA 생활성도 평가)

  • Yang, Mi-Hi;Yoo, Ji-Hyun;Kim, Cheong-Sik;Shin, Ae-Sun;Kang, Dae-Hee;Chang, Soung-Hoon;Park, Sue-Kyung;Shin, Hai-Rim;Yoo, Keun-Young
    • Journal of Preventive Medicine and Public Health
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    • v.36 no.4
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    • pp.373-376
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    • 2003
  • Objectives : Peripheral blood-buffy coat fractions (N=14,956) have been stored at $-70^{\circ}C$ in the headquarter of the Korean Multicenter Cancer Cohort (KMCC), since 1993. To study the future molecular etiology of cancers using specimens of the cohort, properly stored specimens are necessary, Therefore, the DNA-viability of the bully coat samples was investigated. Methods : Buffy coat fraction samples were randomly selected from various collection areas and years (N=100). The DNA viability was evaluate from the UV-absorbent ratios at 260/280nm and the PCH for $\beta$-globin was performed with genomic DNA isolated from the buffy coat. Results : PCR products were obtained from 85 and 98% of the C and H area-samples, respectively, using 50 or $100{\mu}l$ of the buffy coat. There were significant differences in the yields of the PCR-amplifications from the C and H areas (p<0.05), which was due to differences in the homogenization of the buffy coat fractions available as aliquots. The PCR-products were obtained from all of the samples (N=7) stored at the C area-local confer, but the other aliquots stored at the headquarter were not PCR-amplified, Therefore, the PCR products in almost all the samples, even including the DNA-degraded samples, were obtained. In addition, an improvement in the DNA isolation, i,e. approx. 1.6 fold, was found after using extra RBC lysis buffer. Conclusions : PCR products for $\beta$-globin were obtained from nearly all of the samples. The regional differences in the PCR amplifications were thought to have originated from the different sample-preparation and homogenization performance. Therefore, the long term-stored buffy coat species at the KMCC can be used for future molecular studies.

Characteristics of Thermal Variations with the Different Land Covers in an Urban Area (도시 지역에서 토지 피복에 따른 열 변이 특성)

  • Park, Sung-Ae;Kong, Hak-Yang;Kim, Seung-Hyun;Park, Sungmin;Shin, Young-Kyu
    • Ecology and Resilient Infrastructure
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    • v.3 no.1
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    • pp.46-53
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    • 2016
  • This study was conducted to analyze the effect of the different land covers of an urban park (Hyowon park) in downtown Suwon on the urban thermal variations during a hot summer. The effect of the air temperature reduction in the urban park was 4.4%-4.5% for the downtown residence (Maetan-dong). This value was about 0.8% lower than that of the outskirts residence (Sanggwanggyo-dong). The daily mean temperature, daily maximum temperature, summer day and heat wave frequency were measured under the different land covers (cement-block, grass, pine-grass, shading area and mixed forest) showed these values generally decreased under natural land cover types. Daily minimum temperature and tropical night frequency didn't seem to correlate with the land cover types. Means of thermal comfort indices (wet bulb globe temperature, heat index and discomfort index) in the shading area, mixed forest and the pine-grass types were lower than those of cement block and grass types. However the levels of those indices were equal to 'very high' or 'caution' levels in the afternoon (13:00-15:00). In the morning (06:00-08:00), thermal comfort indices of the urban park didn't correlate with land cover types. Therefore, to reduce heat stress and to improve the thermal comfort in urban parks, an increase in the area of natural land cover such as grass, forest and open spaces is required.

Effect of acupuncture treatment on carrageenan-induced inflammation and NADPH-diaphorase reactivity in the hypothalamus of Stat4 knockout mice (Carrageenan 염증 유도된 Stat 4 유전자 제거생쥐의 시상하부에서 NADPH-diaphorase 반응에 대한 침의 영향)

  • Hong, Mee-Suk;Kim, Mi-Ja;Kim, Jin-Ju;Park, Hi-Joon;Chung, Joo-Ho
    • Korean Journal of Acupuncture
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    • v.24 no.4
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    • pp.221-231
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    • 2007
  • 목 적 : 본 연구의 목적은 시상하부에서 침처치에 대한 nitric oxide synthase (NOS)발현을 nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)를 이용한 조직화학 염색법으로 관찰하였다. 실험방법 : 동물은 Balb/c (wild type) 와 Stat 4 knockout (KO) 생쥐를 사용하였다. 염증유도는 1% carrageenan 용액 (20ul/마리)을 발 뒤꿈치 표피에 주사하였고, 침 처치는 족삼리 (ST36)에 시침하였다. 침 처치 후 5시간까지 부종율을 부종측정기로 측정하였으며, 마지막으로 부종을 측정한 후 동물을 희생하여 뇌를 적출하여 고정하였다. 침에 대한 효과를 확인하기 위하여 NADPH-d 반응의 조직염색을 실시하였다. 염증유도와 그룹간의 유의성 검증은 one-way ANOVA를 사용하였다. 결 과 : 대조군인 Balb/c와 실험군인 stat4 KO 생쥐를 carrageenan으로 염증을 유도시에 대조군은 90%이상 유도된 반면, Stat4 KO 그룹은 50% 정도의 염증만이 유도되었다. 염증을 유도한 생쥐의 족삼리에 침 처치시 대조군은 1시간에서 약 40%정도 감소하였고 (P<0.05), Stat4 KO 실험군은 유의한 염증 감소율을 보이지 않았다. 시상하부의 lateral hypothalamic area (LHA)와 paraventricular nucleus (PVN)부위의 침에 대한 효과를 NADPH-d 에 양성으로 반응하는 세포수로 비교하여 다음과 같은 결과를 얻었다. (1) 대조군에서 염증 유도시 시상하부의 PVN는 NADPH-d 양성세포수가 감소하였고, LHA에서는 증가하였다. (2) 염증을 유도한 대조군에 침을 처치시 PVN은 세포수가 증가하였고, LHA에서는 감소하는 경향을 보였다. (3) 염증을 유도한 Stat4 KO 군에서는 시상하부의 PVN과 LHA부위 모두에서 NADPH-d 양성세포수가 감소하였고, 염증유도그룹에 침을 처치시 PVN과 LHA부위 모두에서 세포수가 증가함을 관찰 할 수 있었다. (4) 대조군과 실험군 모두에 salicylic acid로 비교하였더니 염증유도 효과 및 NADPH-d 세포 수에서 침 처치와 비슷한 결과를 나타내었다. 결 론 : 침은 염증을 유도한 생쥐에서 염증 감소에 유의한 효과가 있다. 염증을 유도한 Balb/c 와 Stat4 KO 생쥐에 침을 처치 시 시상하부의 NADPH-d 발현이 LHA부위와 PVN에서 서로 다르게 나타나는 것으로 나타난다. 이러한 현상은 침 효과가 시상하부의 위치에 대한 작용이 다르기 때문이라고 생각된다.

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Transduced Tat-α-Synuclein Protects against Oxidative Stress In vitro and In vivo

  • Choi, Hee-Soon;Lee, Sun-Hwa;Kim, So-Young;An, Jae-Jin;Hwang, Seok-Il;Kim, Dae-Won;Yoo, Ki-Yeon;Won, Moo-Ho;Kang, Tae-Cheon;Kwon, Hyung-Joo;Kang, Jung-Hoon;Cho, Sung-Woo;Kwon, Oh-Shin;Choi, Jin-Hi;Park, Jin-Seu;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.39 no.3
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    • pp.253-262
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    • 2006
  • Parkinson's disease (PD) is a common neurodegenerative disorder and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although many studies showed that the aggregation of $\alpha$-synuclein might be involved in the pathogenesis of PD, its protective properties against oxidative stress remain to be elucidated. In this study, human wild type and mutant $\alpha$-synuclein genes were fused with a gene fragment encoding the nine amino acid trans activator of transcription (Tat) protein transduction domain of HIV-l in a bacterial expression vector to produce a genetic in-frame WT Tat-$\alpha$-synuclein (wild type) and mutant Tat-a-synucleins (mutants; A30P and A53T), respectively, and we investigated the protective effects of wild type and mutant Tat-$\alpha$-synucleins in vitro and in vivo. WT Tat-$\alpha$-synuclein rapidly transduced into an astrocyte cells and protected the cells against paraquat induced cell death. However, mutant Tat-$\alpha$-synucleins did not protect at all. In the mice models exposed to the herbicide paraquat, the WT Tat-$\alpha$-synuclein completely protected against dopaminergic neuronal cell death, whereas mutants failed in protecting against oxidative stress. We found that these protective effects were characterized by increasing the expression level of heat shock protein 70 (HSP70) in the neuronal cells and this expression level was dependent on the concentration of transduced WT Tat-$\alpha$-synuclein. These results suggest that transduced Tat-$\alpha$-synuclein might protect cell death from oxidative stress by increasing the expression level of HSP70 in vitro and in vivo and this may be of potential therapeutic benefit in the pathogenesis of PD.

Comparative Study of Relationship between the Depressive Tendency and Tenderness of Alarm Points and Transport Points (우울 경향과 복모혈(腹募穴), 배유혈(背兪穴)압통과의 관계 비교 연구)

  • Suh, Min-Jung;Kim, Song-Yi;Park, Young-Jae;Jung, Won-Mo;Cha, Su-Jin;Lee, Hyang-Sook;Lee, Hye-Jung;Park, Hi-Joon
    • Korean Journal of Acupuncture
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    • v.27 no.4
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    • pp.97-109
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    • 2010
  • Objective : To examine whether any correlation between tendency towards depression and tenderness at special acupuncture points exists, thus to explore the potential diagnostic property of acupuncture points. Methods : A total 31 subjects were included in this study. They filled out questionnaires about their mental [Beck Depression Inventory (BDI), Stress Response Inventory (SRI), Profile of Mood States (POMS)] and physical (fatigue due to overexertion, and food accumulation) symptoms. Identical weight around Alarm points (CV17, CV12, ST25, CV5, CV4, and LR13) and transport points (BL14, BL20, BL21, BL22, BL25, and BL27) was given using an algometer and the subjects rated their pain on an 11-point numerical rating scale. Heart rate variability (HRV) was also measured. Results : The subjects were divided into two groups, normal and depressive tendency groups with a cut-off point of nine on BDI. The depressive tendency group reported significantly higher values in SRI, POMS, and questionnaire for fatigue due to overexertion. In the pressure pain measurement, depressive tendency group had more pressure pain at CV12, left side of BL20, BL14, BL22 and both sides of BL21, BL25, BL27, significantly (each p<0.05). The data of HRV did not show significant differences between groups. Conclusions : People with a tendency towards depression may be prone to stress, negative mood, and fatigue due to overexertion. In addition, they may be more likely to develop tenderness at alarm points and transport points compared with healthy people. Further research is needed to confirm this finding.

$CO_2$ Buffering and Hydrogen Ion Concentration Gradient across Cell Membrane in Acute Acid-Base Disturbances in Dogs (혈액과 조직의 $CO_2$완충능 및 세포막을 통한 $H^+$농도 경사)

  • Hwang, Sang-Ik;Park, Young-Bae;Min, Byoung-Ku;Kim, Woo-Gyeum
    • The Korean Journal of Physiology
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    • v.17 no.2
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    • pp.119-124
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    • 1983
  • The in vivo and in vitro buffer capacities of true plasma and tissue buffer capaciies were compared on dogs. Intracellular pH was determined on skeletal muscle by a modification of the method of Schloerb and Grantham using $C^{14}$ DMO. The in vivo curve for plasma or extracellular fluid has a much lower slope than the in vitro curve. The in vivo slope of skeletal muscle in the dog is approximately 20 sl. The slope for skeletal muscle in vivo falls between the in vitro and in vivo slopes of true plasma. It appears that intracellular hydrogen ion varies linearly with extracellular hydrogen ion when $CO_2$ tension is changed. Both hydrogen ion gradient and Hi/He ratio vary in skeletal muscle, with an increase in $CO_2$ tension. Infusion of 0.3N HCl gave two distinct patterns, the $H_i-H_e$ gradient decreased; and it would appear that very little hydrogen ion as such penetrated to the inside of the cells during the time of observation. Although lactic acid presumably enters the cell and the same of larger load was given as was used for hydrochloric acid, only very mild intracellular acidosis resulted, ostensibly due to metabolism of this substrate. Gluconic acid produced a more severe acidosis, both intracellularly and extracellularly, but with both of these acids the hydrogen ion gradient decreased and the $H_i/H_e$ ratio also decreased. The experiments on the dogs with hemorrhagic shock the hydrogen ion increase producing the acidosis originates inside the cells. Even so, the hydrogen ion gradient increased only very slightly in the acute experiments. This may suggest that even over short intervals of time skeletal muscle cells have a capacity to pump out hydrogen ions at a rate which maintains approximately the normal $H_i/H_e$ gradient when the source of the hydrogen ion is in the interior of the cell.

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Prebiotic Properties of Levan in Rats

  • Jang, Ki-Hyo;Kang, Soon-Ah;Cho, Yun-Hi;Kim, Yun-Young;Lee, Yun-Jung;Hong, Kyung-Hee;Seong, Kyung-Hwa;Kim, So-Hye;Kim, Chul-Ho;Rhee, Sang-Ki;Ha, Sang-Do;Choue, Ryo-Won
    • Journal of Microbiology and Biotechnology
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    • v.13 no.3
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    • pp.348-353
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    • 2003
  • Generally, two different types of fructose polymer are found in nature. One is inulin, whose fructosyl residues are linked mainly by a ${\beta}-(2,1)-linkage$, while the other is high-molecular-weight levan, whose fructosyl residues are linked mainly by a ${\beta}-(2,6)-linkage$. In contrast to the extensive studies on the prebiotic properties of inulin, there has been no report on the effect of levan on the large bowel microflora in viva. Therefore, to examine whether dietary levan can be used as a prebiotic, Sprague-Dawley male rats were fed one of two diets for 3 weeks: 1) basal diet plus sucrose; 2) basal diet plus 10% (wt/wt) levan. The cecal bowel mass, cecal and colon short-chain fatty acids (SCFAs), pH, and microflora were then compared. The intake of the levan-containing diet significantly increased the total cecal weight and wall weight. The analyses of the SCFAs in the cecal and colonic contents revealed that levan was converted into acetate, butyrate, and lactate, which resulted in acidic conditions. The intake of levan also significantly increased the total number of microorganisms by 5-fold and lactic acid-producing bacteria (LAB) 30-fold in the feces. Accordingly, the current work shows that levan can be used as a prebiotic for stimulating the growth of LAB in an animal model.

Fine mapping of rice bacterial leaf blight resistance loci to major Korean races of Xoo (Xanthomonas oryzae)

  • Lee, Myung-Chul;Choi, Yu-Mi;Lee, Sukyeung;Yoon, Hyemyeong;Oh, Sejong
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.73-73
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    • 2018
  • Bacterial leaf blight(BLB), caused by X. oryzae pv. oryzae(Xoo), is one of the most destructive diseases of rice due to its high epidemic potential. Understanding BLB resistance at a genetic level is important to further improve the rice breeding that provides one of the best approaches to control BLB disease. In the present investigation, a collection of 192 accessions was used in the genome-wide association study (GWAS) for BLB resistance loci against four Korean races of Xoo that were represented by the prevailing BLB isolates under Xoo differential system. A total of 192 accessions of rice germplasm were selected on the basis of the bioassay using four isolated races of Xoo such as K1, K2, K3 and K3a. The selected accessions was used to prepare 384-plex genotyping by sequencing (GBS) libraries and Illumina HiSeq 2000 paired- end read was used for GBS sequencing. GWAS was conducted using T ASSEL 5.0. The T ASSEL program uses a mixed linear model (MLM). T he results of the bioassay using a selected set of 192 accessions showed that a large number of accessions (93.75%) were resistant to K1 race, while the least number of accessions (34.37%) resisted K3a race. For races K2 and K3, the resistant germplasm proportion remained between 66.67 to 70.83%. T he genotypic data produced SNP matrix for a total of 293,379 SNPs. After imputation the missing data was removed, which exhibited 34,724 SNPs for association analysis. GWAS results showed strong signals of association at a threshold of [-log10(P-value)] more than5 (K1 and K2) and more than4 (K3 and K3a) for nine of the 39 SNPs, which are plausible candidate loci of resistance genes. T hese SNP loci were positioned on rice chromosome 2, 9, and 11 for K1 and K2 races, whereas on chromosome 4, 6, 11, and 12 for K3 and K3a races. The significant loci detected have also been illustrated, NBS-LRR type disease resistance protein, SNARE domain containing protein, Histone deacetylase 19, NADP-dependent oxidoreductase, and other expressed and unknown proteins. Our results provide a better understanding of the distribution of genetic variation of BLB resistance to Korean pathogen races and breeding of resistant rice.

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