• Journal of Gastric Cancer
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• 제13권3호
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• pp.172-178
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• 2013

Purpose: The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-${\alpha}$ and -${\beta}$ mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of the cell lines. Materials and Methods: Detection of estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with $17{\beta}$-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test. Results: Estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, $17{\beta}$-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-${\alpha}$ nor estrogen receptor-${\beta}$ antagonist blocked the anti-proliferative effect of $17{\beta}$-estradiol. Conclusions: Our results indicate that estrogen receptor-${\beta}$ mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-${\beta}$ positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

• 대한간호학회지
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• 제30권1호
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• pp.18-28
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• 2000

The Purpose of this study is to extend the understanding and knowledge of menopause by comparing menopausal symptoms of married women and nuns in order to improve health and the quality of life for women. In this study a questionnaires were distributed to 116 nuns and 121 married women, from forty to fifty nine years old in Daegu metropolitan city. This study used the measurement of menopausal symptoms (Cronbach's Alpha=0.96) corrected and complemented by this student with consideration of various literature centered around menopausal symptoms, suggested by Janette M. Perz as 51 questions including 4 realms; [mental psychological factors], [physical physiological factors], [eyesight factors], and [urinary generative factors] in order to measure the degree of menopausal symptoms. The results are as follows : 1. There was a significant difference between educational background, religion, occupation, leisure time, satisfaction of marriage or ascetic life, existence of hormonal treatment, name of medical operation, and existence of counselling about menstruation as general and physiological characteristics of the nuns' group and the married women's group. 2. The menopausal symptoms of the nuns' group and the married women's group according to order in which they were presented were; 'feeling tired and lacking in energy(1.71 points)' 'vision not clear or clouded(1.69 points)', and 'be forgetful (1.57 points)' in nuns' group. 'be forgetful (1.87 points)', 'vision not clear or clouded(1.83 points)' and 'feeling tired and lacking in energy(1.76 points)' in the married women's group. The symptoms which showed the highest rank of menopausal symptoms had a maximum score of 4 points. 3. There was a statistical a significance (t=-3.9807, p<.0001) between the two groups which showed, on an average, 57.92 points in the married women's group and 43.03 points in the nuns' group from 0 to 196 of the possible points of menopausal symptoms. In difference of menopausal symptoms by menstrual aspect of the nuns' group and the married women's group, there was statistically significant difference between the two groups, showing 44.81±26.07 score in the nuns' group and 72.33±35.29 score in the married women's group as the mean score of the groups with no menstruation(t=-4.1132, p=0.0001). 4. The differences in menopausal symptoms with respect to the general and physiological characteristics of the nuns' group and the married women's group were that the nuns' group showed less menopausal symptoms on all the items than that of the married women's group. Finally, in these results, the married women's group showed higher menopausal symptoms than that of the nuns' group. Especially as the score of menopausal symptoms since the climacteric was very high it is confirmed to be a new phenomenon. Accordingly, it is considered to be necessary to carry out an indepth study of the factors related to establishing a strategy for nursing service.

• 한국환경성돌연변이발암원학회지
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• 제22권2호
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• pp.65-69
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• 2002

To elucidate the effect of microsphere coinjection on the administration of oligodeoxynucleotides (ODN), we have investigated biodistribution of ［S-35］-labeled antisense ODN targeted to cAMP-dependent protein kinase (PKA) RI-$\alpha$ subunit in nude mice xenografted with WiDr (human colon cancer, ATCC CCL218). The strategy of using microsphere has been proposed for cancer treatment as a carrier of therapeutic ODN so that it could offer an advantage with respect to maintaining constant ODN levels in blood and obtaining higher therapeutic ODN concentration at tumor sites. Comparative biodistribution studies were performed in nude mice (female, 20 g of body weight, n = 4-6) xenografted with WiDr cancer cells, when 0.1 $\mu$Ci (specific activity, 2.94 mCi/$\mu$mole) of ［S-35］-labeled RI-$\alpha$ antisense ODN was injected alone or with microsphere (PLG-18, polylactic copolymer with cationic surfactant DDAB18). Peak tumor uptake of ［S-35］-labeled ODN was significantly increased from 17.7% (at 6 h) of injected dose per gram of tissue (ID/g) to 42.5% (at 24 h) ID/g when microsphere was coinjected with ODN. The different biodistribution in the kidney accumulation (e.g., 100.2% ID/g for ODN alone and 54.9%/ID/g for microshpere coinjection) may contribute to higher blood concentration (e.g., 21.5%ID/$m\ell$ for ODN alone and 37.5%ID/$m\ell$ for microsphere coinjection) of radiolabeled ODN. Of importance is the fact that the whole body retention of radioactivity increased with microsphere coinjection from 50.8%ID/g to 68.0%ID/g after 24-h of injection. This decreased kidney accumulation and increased whole body retention of ［S-35］-labeled ODN resulted in a significant improvement of ODN targeting to the tumor site. In conclusion, the coinjection of microsphere appears to be an important carrier system in vehiculation of antisense oligonucleotide to the tumor tissue in vivo.

• Tuberculosis and Respiratory Diseases
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• 제79권1호
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• pp.22-30
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• 2016

Background: The purpose of this study was to document outcomes following withdrawal of a single inhaler (step-down) in chronic obstructive pulmonary disease (COPD) patients on triple therapy (long-acting muscarinic antagonist and a combination of long-acting ${\beta}2$-agonists and inhaled corticosteroid), which a common treatment strategy in clinical practice. Methods: Through a retrospective observational study, COPD patients receiving triple therapy over 2 years (triple group; n=109) were compared with those who had undergone triple therapy for at least 1 year and subsequently, over 9 months, initiated inhaler withdrawal (step-down group, n=39). The index time was defined as the time of withdrawal in the step-down group and as 1 year after the start of triple therapy in the triple group. Results: Lung function at the index time was superior and the previous exacerbation frequency was lower in the step-down group than in the triple group. Step-down resulted in aggravating disease symptoms, a reduced overall quality of life, decreasing exercise performance, and accelerated forced expiratory volume in 1 second ($FEV_1$) decline ($54.7{\pm}15.7mL/yr$ vs. $10.7{\pm}7.1mL/yr$, p=0.007), but there was no observed increase in the frequency of exacerbations. Conclusion: Withdrawal of a single inhaler during triple therapy in COPD patients should be conducted with caution as it may impair the exercise capacity and quality of life while accelerating $FEV_1$ decline.

• 대한의생명과학회지
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• 제12권3호
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• pp.289-301
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• 2006

Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.

• 생명과학회지
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• 제30권8호
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• pp.661-671
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• 2020

항암 요법의 실패의 주요 원인으로 암세포의 항암제에 대한 내성 획득이 잘 알려져 있다. 비스테로이드소염제(NSAID)는 항염증작용뿐만 아니라 항암제와의 병용요법으로 임상적인 암 치료 요법에 응용되고있다. 본 연구에서는 NSAIDs 인 celecoxib 및 이의 구조 유사체인 2,5-dimethyl celecoxib 그리고 ibuprofen의 인간 암세포에 대한 imatinib 및 TNF-related apoptosis inducing ligand (TRAIL) 세포 독성 변화에 미치는 영향을 조사하였다. NSAID는 TRAIL 및 imatinib에 각각 약제 내성을 나타내는 간암 세포와 백혈병 세포에서 이들 약물의 세포독성을 증강시키는 활성을 나타내었다. NSAID는 ATF4/CHOP의 발현 증강으로 소포체 스트레스 및 오토파지(Autophagy, 자가포식)를 유도하였다. 이로 인한 DR5 발현 증강과 함께 c-FLIP 발현 억제로 TRAIL의 세포독성을 증강시키는 기전을 나타내었다. NSAID로 유도되는 오토파지 활성은 imatinib-resistant CD44^highK562 백혈병세포의 imatinib 감수성을 증강시켰으며, NSAID는 이 세포에서 높은 발현을 나타내는 다양한 stemness-related marker 단백질의 발현 감소를 촉진시키는 활성으로 세포사멸을 유도하는 것을 알 수 있었다. 이러한 결과는 NSAID의 오토파지 유도 활성이 TRAIL과 imatinib의 세포 독성을 증강시키는 것으로서, NSAID와 이들 약물과 병용 처리방법은 인간 암세포의 TRAIL 및 imatinib 내성을 극복 시킴과 동시에 암세포에 이들 약물의 독성 부작용을 감소시킬 수 있는 낮은 농도의 처리를 가능하게 할 것으로 사료된다.

• 식물병연구
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• 제17권2호
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• pp.142-147
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• 2011

친환경 미생물제제를 이용하여 개발된 방제프로그램에 의해 토마토 잎곰팡이병에 대한 효과를 검정하였다. 2010년 4월부터 7월까지 시설내에서 토마토 잎곰팡이병은 약 13.1% 발생하였다. PDA 배지에서 잎곰팡이병원균의 균사 생장을 50% 이상 억제한 친환경유기농자재 7종을 선발하였다. 선발된 4종 병해관리용 유기농자재는 온실에서 50% 이상의 방제효율을 나타냈으며, 최종적으로 Bacillus subtilis GB-0365와 B. subtilis KB-401 2종은 토마토 정식 20일부터 70일까지 4회 살포시 71.8% 이상의 방제효과를 나타냈으며, 3회 처리시에는 79.3%의 우수한 방제효과를 나타냈다. 따라서 토마토 친환경 유기재배농가를 위해 선발된 친환경농자재와 시기에 따른 살포방법에 의한 방제프로그램은 효율적인 모델로 이용 가능할 것으로 기대된다.

• 생명과학회지
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• 제14권5호
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• pp.874-881
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• 2004

혈관 신생은 암의 성장 및 전이뿐만 아니라 염증, 관절염, 건성, 동맥경화 등의 병적인 진행에 주요한 역할을 하며, 혈관신생 억제를 통한 암의 치료를 시도하는 연구들이 활발하게 진행되고 있다. 혈관 신생 시 내피세포의 증식, 이동을 유도하는 활성화 과정이 필수적으로 일어나는 것으로 알려져 있다 본 연구에서는 in vitro에서 내피세포를 배양하여, 각종 growth factor가 풍부한 배지에서 활성화 시켰을 때, 그렇지 않는 세포들과의 유전자 발현 형태를 비교 조사하였다. HUVEC을 70∼80% cofluency로 배양시킨 후에 endothelial cell growth supplement (ECCS), 20% fetal bovine serum, heparin이 첨가된 Ml99 배지에서 13 시간 활성화시킨 세포(AHUVEC)와 대조군 세포(RHUVEC)로부터 분리한 total RNA로부터 CDNA를 제작하였고, 이것을 18,864 개의 유전자가 올려져있는 인간 올리고 칩과 hybridization 반응을 시켰다. 반응된 유전자를 이용하여 random clustering분석을 실시한 결과, 활성화 시켰던 HUVEC과 그렇지 않은 HUVEC으로 dendrogram 상에서 두개의 subgroup으로 나뉘어 지는 것을 확인할 수 있었다. 최소 2배 이상 발현 변화가 있는 유전자 122종이 활성화 시켰던 HUVEC으로부터 추출되었다. 이중에서 기능이 알려진 32 개의 유전자는 활성화시킨 HUVEC에서 발현이 증가하였고, 38 개의 유전자 발현은 감소하였다. 흥미롭게도 세포 증식과 이동, 염증, 면역반응에 관련한 유전자의 발현이 증가된 반면에 세포 흡착과 혈관 조직과 기능에 관련한 유전자의 발현이 감소된 것이 관찰되었다. 예상외로 규명이 잘된 혈관신생 인자와 관련한 유전자들의 발현에는 크기 차이를 보이지 않았으나, Eph-B4의 발현은 약 4 배 감소된 것으로 관찰되었다 또한, 2배 이상 발현에 차이를 보이고 기능이 알려져 있지 않은 유전자 52종이 발견되었다. 따라서, 이러한 연구 결과로부터 새로운 혈관 표적 물질 개발에 대한 기회가 제공될 수 있을 것이라 사료된다.

• 생명과학회지
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• 제19권10호
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• pp.1360-1367
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• 2009

간섬유화는 지속적인 간세포 손상에 대한 수복현상으로 일어나며, 급성 염증반응과 같은 손상이 주어진 후에는 간세포의 괴사 및 세포외기질의 축적이 일어나게 된다. 간섬유화에 대한 새로운 치료방법을 모색하기 위하여 본 연구에서는 간섬유화 과정에서 염증 반응과 관련된 NF-$\kappa$B와 세포외기질의 축적과 관련된 Sp1전사인자를 동시에 조절하여 간섬유화 억제효과를 관찰하고자 하였다. 전사인자인 Sp1과 NF-$\kappa$B를 동시에 억제하기 위하여 한 분자 내에 Sp1과 NF-$\kappa$B의 전사인자와 결합하는 부위를 가지는 Chimeric (Chi) decoy oligodeoxynucleotide (ODN)을 제작하였다. Chi decoy ODN은 활성화된 간성상세포에서 간섬유화 와 관련된 유전자 발현을 억제시켰으며, 섬유화 동물모델에서도 간 조직의 염증 반응 및 섬유화 관련 인자의 발현을 현저히 억제시켰다. 따라서 Chi decoy ODN은 간섬유화 및 활성화된 간성상세포의 활성을 억제할 수 있는 유전자 치료제로 고려될 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1299-1308
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• 2016

Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.