Silibinin Inhibits Tumor Growth through Downregulation of Extracellular Signal-Regulated Kinase and Akt <i>in Vitro</i> and <i>in Vivo</i> in Human Ovarian Cancer Cells

Cho, Hyun Jin,Suh, Dong Soo,Moon, Soo Hyeon,Song, Yong Jung,Yoon, Man Soo,Park, Do Yoon,Choi, Kyung Un,Kim, Yong Keun,Kim, Ki Hyung American Chemical Society 2013 Journal of agricultural and food chemistry Vol.61 No.17

<P>Anticancer activity of silibinin, a flavonoid, has been demonstrated in various cancer cell types. However, the underlying mechanisms were not elucidated in human ovarian cancer cells. The present study was undertaken to examine the effect of silibinin <I>in vitro</I> and <I>in vivo</I> on tumor growth in human ovarian cancer cells. Silibinin decreased cell viability in a dose- and time-dependent manner. Silibinin caused an increase in reactive oxygen species (ROS) generation, and the silibinin-induced cell death was prevented by the antioxidant <I>N</I>-acetylcysteine (NAC). Western blot analysis showed silibinin-induced downregulation of extracellular signal-regulated kinase (ERK) and Akt. Transfection of constitutively active forms of MEK and Akt prevented the silibinin-induced cell death. Oral administration of silibinin in animals with subcutaneous A2780 cells reduced tumor volume. Subsequent tumor tissue analysis showed that silibinin treatment induced a decrease in Ki-67-positive cells, an increase in transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, activation of caspase-3, and inhibition of p-ERK and p-Akt. These results indicate that silibinin reduces tumor growth through inhibition of ERK and Akt in human ovarian cancer cells. These data suggest that silibinin may serve as a potential therapeutic agent for human ovarian cancers.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2013/jafcau.2013.61.issue-17/jf400192v/production/images/medium/jf-2013-00192v_0008.gif'></P>

Gelatin 액화세균의 생장억제에 관한 연구

이기성,崔榮吉,趙賢淑 漢陽大學校 環境科學硏究所 1983 環境科學論文集 Vol.4 No.-

Gelatin 을 재료로 이용하는 식품의 폐기물에서 gelatin 을 액화시키는 능력이 특히 뛰어난 4종의 세균을 분리·동정하였으며, 배지내에 NaCI, KI·I₂, CuSO₄등의 억제제를 농도별로 처리했을때 나타나는 4균주의 생존도 및 액화능의 변화를 비교·검토하였고, 생존도에 미치는 pH의 영향도 조사하였다. 또한 MIC(Minimal Inhibitory Concentration) Test를 시행하여 항생제에 대한 4균주의 MIC도 조사하였다. 그 결과는 다음과 같다. 1. 4균주중 H strain은 Serratia liquefaciens로, Y₁strain은 Enterobacter속으로, Y₂와 Y₃strain 은 Pseudomonas 속으로 동정되었다. 2. 배지내에 억제제로 NaCl을 처리했을 경우, 7% 농도에서 생장이 100% 억제되었으며, KI·I₂처리시에는 20ppm 에서부터 생장이 억제되기 시작하여 100ppm에서는 4개의 균주 모두 100% 생장이 억제되었다. CuSO₄처리시에는 100ppm에서부터 억제효과를 나타내기 시작하여 300ppm에서는 거의 100% 억제 효과를 보였다. 생존도에 미치는 pH의 영향을 살펴본 결과, pH 5.0, 5.5, 6.0에서는 대조군과 동일한 생존도를 나타냈으나 pH 4.0, 4.5 에서는 100% 생장이 억제되었다. 분리 균주들의 액화능 비교에 있어서는 H strain 이 가장 뛰어난 액화능을 나타내었다. CuSO₄와 KI·I₂를 각각 3ppm, 10ppm의 저농도로 처리했을 경우 4균주의 액화능은 대체로 10∼20% 감소되었다. 3. 액화 능력이 가장 뛰어난 H strain 의 MIC 는 Penicillin G; 1∼5 ㎍/ml, Spectinomycin; 12.5∼25㎍/ml, Ampicillin; <0.05㎍/ml, Cefobid; <1㎍/ml, Claforan; 0.02∼0.3㎍/ml, Tetra-cycline; >10㎍/ml로 나타났다. Tetracycline을 제외한 5가지 항생제에 대하여 H strain이 Y strain들에 비해 민감한 것으로 나타났다. 그러나 Tetracycline의 경우에는 H strain이 Y strain들에 비하여 저항성을 갖는 것으로 나타났다. Four strains of gelatin-liquefying bacteria were isolated from the sewage of the food using gelatin as the material. Treated with various concentration of NaCl, KI-I₂and CuSO₄in the culture medium and with various gradient of pH, viability of the four strains was examined and compared with each other. And also, gelatin liquefying ability was investigated in the normal culture condition and in accordance with the concentration of the inhibitor. Morever, MIC(Minimal Inhibitory Concentration) test for these strains was also carried out. The results were as follows: 1. Of the four isolated strains, the H strain was identified as Serratia liquefaciens, Y₁as the genus Enterobacter, Y₂and Y₃strains as the genus Pseudomonas. 2. Treating the culture medium with NaCl as the growth inhibitor, 7% concentration of NaCl inhibited completely the viability of all the isolated strains. Adding KI-I₂solution to the medium at the level of 20ppm, viability began to decrease and the inhibitory effect was shown 100% at 100ppm. Treated with CuSO₄at the level of 10ppm, viability began to decrease, and at 300ppm growth inhibition showed almost 100%. There was no significant difference in viability according to the pH gradient at the range of 5.0-6.0. However, at pH 4.0 and 4.5, 100% inhibitory effect on the growth was shown. Considered with the ability of gelatin liquefaction, the H strain among the four strains had the most rapid and strong ability in gelatin liquefaction. (That is, about 23 times more effective in gelatin liquefaction than that of Y₁strain) 3. Considered the MIC test, the H strain was more sensitive to Penicillin G(1-5 ㎍/ml), Spectinomycin(12.5-25㎍/ml), Ampicillin(<0.05㎍/ml), Cefobid(<1㎍/ml) and Claforan (0.02-0.3㎍/ml) than to those of the strains. Compared with the other strains, the H strain was more insensitive up to the level of 10㎍/ml to the minimal inhibitory concentration of Tetracycline.

Expression Profiles of Retinoblastoma Protein and p27Kip1 According to HER2 Amplification Status in Primary Breast Cancer

신재호,Sung-Jin Park,Hyun-Jin Cho,Geumhee Gwak,Byung-Noe Bae,Ki Whan Kim,Hong-Yong Kim2,Kyeongmee Park,Sehwan Han 한국유방암학회 2009 Journal of breast cancer Vol.12 No.1

Purpose: Human epidermal growth factor receptor-2 (HER-2)/neu amplification affects the cell proliferation through the modulation of multiple G1 cell cycle regulators in breast tumor cells. We performed this study to investigate whether retinoblastoma protein (pRB) and p27Kip1 were differently expressed according to the HER2 amplification status in human breast cancer. Methods: HER2 amplification was assayed by fluorescence in situ hybridization and the expression of cell cycle regulators were assayed by immunohistochemistry on 153 consecutive invasive breast cancers. The proliferative activity of breast cancer was analyzed according to the HER2 amplification and cell cycle protein expression status. Results: HER2 amplification was observed in 39 (25.5%) of 153 breast cancers. In the HER2 amplified breast cancers, the pRB expression was significantly increased (p=0.011) whereas there was no significant relationship between HER2 amplification and p27Kip1 expression. There was an inverse correlation between pRB expression and Ki-67 labeling index in the HER2 amplified breast cancers (p=0.036). In contrast, Ki67 labeling index was significantly decreased as p27Kip1 expression increased in HER2 non-amplified breast cancers (p=0.028). In HER2 non-amplified breast cancers, we could not observe any association between the pRB expression and Ki67 labeling index. Conclusion: The proliferation of the breast cancers was associated with pRB expression in HER2 amplified tumors whereas it was associated with p27Kip1 expression in HER2 non-amplified tumors. The results of the current study indicate that the cell proliferative activity of the breast cancer is under different growth signal pathways according to HER2 amplification status.

Systemic administration of low dosage of tetanus toxin decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

Bing Chun Yan,In Hye Kim,Joon Ha Park,Ji Hyeon Ahn,Jeong-Hwi Cho,Bai Hui Chen,Jae-Chul Lee,Jung Hoon Choi,Ki-Yeon Yoo,Choong Hyun Lee,Jun Hwi Cho,Jong-Dai Kim,Moo-Ho Won 한국실험동물학회 2013 Laboratory Animal Research Vol.29 No.3

In the present study, we investigated the effect of Tetaus toxin (TeT) on cell proliferation and neuroblast differentiation using specific markers: 5-bromo-2-deoxyuridine (BrdU) as an exogenous marker for cell proliferation, Ki-67 as an endogenous marker for cell proliferation and doublecortin (DCX) as a marker for neuroblasts in the mouse hippocampal dentate gyrus (DG) after TeT treatment. Mice were intraperitoneally administered 2.5 and 10 ng/kg TeT and sacrificed 15 days after the treatment. In both the TeT-treated groups, no neuronal death occurred in any layers of the DG using neuronal nuclei (NeuN, a neuron nuclei maker) and Fluoro-Jade B (F-J B, a high-affinity fluorescent marker for the localization of neuronal degeneration). In addition, no significant change in glial activation in both the 2.5 and 10 ng/kg TeT-treated-groups was found by GFAP (a marker for astrocytes) and Iba-1 (a marker for microglia) immunohistochemistry. However, in the 2.5 ng/kg TeT-treated-group, the mean number of BrdU, Ki-67 and DCX immunoreactive cells, respectively, were apparently decreased compared to the control group, and the mean number of each in the 10 ng/kg TeT-treated-group was much more decreased. In addition, processes of DCX-immunoreactive cells, which projected into the molecular layer, were short compared to those in the control group. In brief, our present results show that low dosage (10 ng/kg) TeT treatment apparently decreased cell proliferation and neuroblast differentiation in the mouse hippocampal DG without distinct gliosis as well as any loss of adult neurons.

Latex Modified Concsdrete 교면공법을 이용한 포장공법의 Life Cycle Cost 분석

조효남,최현호,정평기,이상윤 漢陽大學校 工學技術硏究所 2001 工學技術論文集 Vol.10 No.-

라텍스 개질 콘크리트(Latex Modified Concrete : 이하 LMC라 약칭함)는 방수성, 동결성 등에서 뛰어난 재료이기 때문에 과거 35년 전부터 전 세계적으로 널리 이용되고 있는 포장재료이다. 그러나 아직 국내에서는 고가의 초기공사비 부담으로 인하여 시공실적이 전무한 실정이다. 따라서, 본 연구에서는 현재 우리나라에서 초기도입단계에 있는 라텍스 개질 콘크리트 교면 포장공법을 위한 LCC 분석 절차 및 사용자비용 모델을 제안하고자 하였고, 이러한 절차 및 모델에 기초하여 실제 대상교량의 포장공사에 적용하여 LMC의 LCC 측면에서의 비용 절감효과를 정량적으로 조사하고자 한다. Latex Modified Concrete(LMC) has been widely used for the pavement of highway bridges over the past 35years around the world since it is more resistant to the intrusion of chloride ions, has higher tensile, compressive, and flexural strength, and has greater freeze-thaw resistance. However, in Korea, it has not been introduced to fields due to higher initial construction cost for its overlay than conventional pavement materials. Due to durable characteristics, it should be noted that the LMC may be more cost-effective than conventional pavements such as asphalt pavement considering life-cycle cost(LCC) concept. The objective of this study is intended to suggest a practical LCC analysis model for pavement projects and to demonstrate relative cost-effectiveness of the LMC overlays in comparison with conventional pavement techniques. It may be stated that the procedure proposed in this study may be utilized for making optimal decision on cost-effective pavement design.

외상성 뇌손상 환자에서 발생한 이소성 골화증에 의한 슬개 정맥 압박증 -증례 보고

조홍구,문기현,최은,이양균 순천향의학연구소 1995 Journal of Soonchunhyang Medical Science Vol.1 No.2

Heterotopic ossification is frequent complication in patients with spinal cord or brain injury, although the etiology is unknown. The extensive heterotopic ossification is a cause of limitation of active or passive joint motion and ultimately bony ankylosis which interferes independency in activities of daily living and ability of maximum rehabilitation. Whereas, the articular complication of heterotopic ossification have been well documented, the vascular complication are less well known. We experienced one case with vascular compression and obstruction by heterotopic ossification in a patient with traumatic brain injury and reported the case with clinical and radiologcal and laboratoric findings.

개 비장 질환의 미세세침흡입술을 통한 세포병리학 검사 4례

김현아,윤기영,최호정,정성목,이영원,조성환,박성준 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2011 動物醫科學硏究誌 Vol.18 No.1

To evaluate the accuracy and diagnostic significance of cytopathological diagnosis of canine splenic disorders, cytopathological examination throgh fine-needle aspiration(FNA) referred to Veterinary Medical Teaching Hospital of Chungnam National University were retrospectived. Splenic neoplasm, hemolymphatic neoplasm, hyperplasia, extramedullary hematopoiesis and splenitis were diagnosed canine splenic disorders through cytopathological examination. The patient should be identified what coagulation profile are normal before aspiration, because complication such as hemorrhage could happen. The 4 cases were identified symmetric, asymmetric splenomegaly on abdominal ultrasonography and then were performed ultrasound-guided FNA. The 4 cases were diagnosed hemangiosarcoma(2), hyperplasia(1) and extramedullary hematopoiesis(1) by clinical signs, hematological examination, and cytopathological examination. Cytopathological examination through FNA was cost-effective, no gneral anesthesia, no complication, and non-invasive method of diagnosis for canine splenic disorders.

한국産 황어의 종묘생산에 관한 연구 1. 産卵習性 및 初期生活史

조재권,오성현,노병율,한경호,성기백,박준택 麗水大學校 産業基術硏究所 1999 産業基術硏究所 論文集 Vol.8 No.-

강원도 양양군에 위치한 남대천과 전라남도 섬진강에 분포하고 있는 황어의 종료생산을 위한 기초자료로 産卵習性과 初期生活史에 관하여 관찰한 결과는 다음과 같다. 황어의 産卵期는 자연상태에서 3∼6月이고, 産卵은 흐르는 하천의 자갈 밑에 하였으며, 受精된 卵은 작은 자갈의 표면에 붙어있었다. 알의 크기는 2.70∼3.20㎜(평균 3.00㎜)로 油球는 없었다. 孵化는 평균 사육수온 10.60℃에서 受精 後 300시간부터 시작되었으며, 312시간만에 완료되었다. 孵化 直後의 仔魚는 전장 6.35∼6.87㎜(평균 10.67㎜)로 난황이 거의 흡수되어 後期仔魚期로 접어들며, 입과 항문이 열려있었다. 孵化 後 7∼9일째 後期仔魚는 전장 11.35∼12.30㎜(평균 11.65㎜)로 등지느러미가 생길 부분이 융기하기 시작하였다. 孵化 後 12∼13일째 개체는 전장 12.65∼13.15㎜(평균 12.80)로 이때부터 Daphnia sp.와 Brachionus plicatilis를 攝餌하였으며, 성장이 다소 빨라졌고, 脊索의 끝부분은 45°위로 굽어져 있었다. 孵化 後 43∼45일째의 개체는 전장이 19.55∼22.85㎜(평균 21.95㎜)로 모든 지느러미 줄기가 정수에 달하여 稚魚期로 이행하였다. 孵化 後 50∼52일째의 稚魚들은 전장이 21.54∼27.35㎜(평균 24.55㎜)로 몸의 형태, 체색 및 옆줄이 완전하게 형성되어 成魚에 닮아 있었다. The spawning behavior and early life history of sea rundace, Tribolodon hakonensis were studied. Spawning of T. hakonensis occurs enmasse on bottoms of stream with a spawning season of March to June. The eggs are attached to the under surface of the gravel. The eggs riped were demersal and adhesive, and their diameter were 2.70∼3.20㎜(mean 3.00㎜). Hatching was started at 300 hours after fertilization at mean water temperature 10.60℃. Newly-hatched larvae were 6.35∼6.87㎜ in total length(TL, Mean 6.65㎜), and mouth and anus were not yet opened. 4∼5 days old larvae transformed to postlarva stage and they were 10.25㎜∼11.15㎜ in TL (mean 10.67㎜). As yolk sac were nearly absorbed, mouth and anus were opened. In 7∼9 days after hatching, total length 11.35∼12.30㎜(mean 11.65㎜). The part of the fin-fold at dorsal fin became high. 12∼13 days old larvae were 12.65∼13.15㎜ in TL(mean 12.80㎜), and they fed Daphnia sp. and Brachionus plicatilis actively. In this time the growth rate slightly increased and tip of notocord was flesed on upward. Aggregate numbers of all fin rays were completed at over 19.55∼22.85㎜ in TL(43∼45 days after hatching), at which time the larvae reached the juvenile stage. 50∼52 days old larvae(21.54∼27.35㎜ in TL) were similar in body from, lateral line and color with adult.

선천성 관동정맥루의 경피적 경도관 Coil 색전 1례

조준식,김동수,서정기,장양수,김현승,이도연 대한순환기학회 1997 Korean Circulation Journal Vol.27 No.9

산업용 차량의 유압측정 장비 개발

조기현,백이,이정택 東洋大學校 産業技術硏究所 2002 東洋大學校 産業技術硏究所 論文集 Vol.4 No.1