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.

산발성 장형 위선암 환자의 Microsatellite Instability와 병리학적 양상

조창희,홍유찬,안지현,최경현,이상호,신영명,윤기영,정민정,장희경 고신대학교의과대학 2007 고신대학교 의과대학 학술지 Vol.22 No.2

Background : Through many researches, microsatellite is expected to be a good diagnositic and prognostic factor in colorectal cancer, endometrial cancer, gastric cancer, and the others. The prevalence of microsatellite instability (MSI) in gastric carcinoma has reported variously, 13~44%. Purpose : We aimed to determine the prevalence of MSI-high and the relationship between MSI and pathological characteristics of sporadic intestinal type adenocarcinoma of stomach. Material and Methods : We analyzed 106 sporadic intestinal type adenocarcinoma specimens excised from patients who were over thirty-five years old to determine the statue of microsatellite by DNA sequencing. The tissues were formalin-fixed and paraffin embedded. DNA were extracted and amplified by polymerase chain reaction (PCR). MSI was determined using five markers recommended by National Cancer Institute (NCI). Specimens were also studied with five patholical factors-differenciation of tumor cells, depth of invasion, lymph node metastasis, vessel invasion, and perineural invasion- to determine pathological state. Result : The microsatellite statue was determined as MSI-High in 5 cases (4.7%), no MSI-low, and MSS (microsatellite stable) in 101 cases (95.3%). Within the frequency, there was no large gap in the distinction of gender in MSI cases, but in MSS cases, there was three-times more cases in male. MSI cases had moderate-to-poor differenciation and trend to invade toward serosa. All MSI cases showed no perineural invasion. But we could not find any statistical significance between MSI and pathological characteristics of sporadic intestinal type adenocarcinoma. Conclusion : Results suggest that MSI can not make any certain pathological significance in sporadic intestinal type adenocarcinoma. Even though less than 5% of sporadic intestinal type adenocarcinoma patients showed MSI, it can be used as a influential prediagnostic factor of gastric cancer. Further study with large scale of cases will be followed to verify these results.

스마트폰 부재와 분실을 대비한 어플리케이션

조시현;문상수;김기환;도민균;서재현;김태공 인제대학교 2012 仁濟論叢 Vol.27 No.1

Recently, as the Smart Phone is rapidly disseminated worldwide, it is emerging as an important digital communication media changing the communication types of users. We use the Smart Phone in all aspect of daily life besides communication. The Smart Phone is indispensible tool that has a great ripple effect on our daily life. Therefore, if the Smart Phone users lose or do not bring their phones, they were troubled. In this paper, we make users available to use the Smart Phone, even if they lose or do not bring their phones. To do this end, we develop features that search the phone in case of not knowing where it is, that contact another phone in case of not bringing their phone, that lock the phone in case of losing it. We expect these features promote a expansion and a vitality of the Smart Phone market.

세침 흡인술을 이용한 종창된 림프절의 세포학적 평가

백강현,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

Fine needle aspiration(FNA) cytology is considered as the diagnostic technique of choice in the assessment of swellen lymph nodes. The aim of this study is to determine the indication and diagnostic method of FNA of lymph node lesions performed at Veterinary Medicine Teaching Hospital of Chungnam National University. The records of 16 patients which had undergone FNA during the study period were retrieved. The cytological results were classified as lymphadenitis, lymphoid hyperplasia and lymphoma. Lymphoma cases were classified as B-cell origin and T-cell by immunophenotyping. The result of the FNA cytological diagnosis showed that nine (56%) of the patients were lymphoma, five (31%) of the patients were lymphoid hyperplasia and two (13%) of the patients were lymphadenitis.

正常家兎의 總輸膽管內 揷管을 通해 投與한 Ethyl Alcohol과 Ethyl Ether가 肝實質에 미치는 影響

趙顯默,孫基燮 충남대학교 의과대학 지역사회의학연구소 1982 충남의대잡지 Vol.9 No.1

The retained stones and flukes in the biliary system are still vexing to mcst surgeons because of its considerable morbidity and mortality. For the purpose of removing the retained stones and flukes in the biliary system nonsurgically, many authors have performed T-tube irrigations with physiochemical solutions such as ethyl alcohol, ethyl etherethyl alcohol(2:1), ethyl ether, heparin, 0.01% benzalkonium chloride solution and other solutions. This study was undertaken to investigate the effects of physiochemical agents 〔0.9% NaCl solution, ethyl alcohol (25% & 50%), ethyl ether-ethyl alcohol, ethyl ether solution〕 on liver tissues of healthy rabbits. The capacity of the bile duct system of normal rabbits(weight: 2.8±0.5kg) was estimated by infusion of Biligrafin(75%) through catheters in common bile duct. A polyethylene catheter of gauge No. 20 was inserted into the common bile duct of each rabbit, then 2 ㏄ of 0.9% physiologic saline solution, ethyl alcohol solution(25% & 50%), ethyl ether-ethyl alcohol solution, ethyl ether solution were infused through the catheter in each group. From six days after the operation, physiochemical agents were infused through catheter in common bile duct once a day (total number of infusion in each group: 2,5,10,15,30 times). The rabbits were sacrificed for the study of the histopathological findings of the liver, and the following results were obtained:1. In the control group which was administered ten times of 2cc of 0.9% sodium chloride solution, the histopathological changes appeared for the first time in the form of mild focal necrosis in hepatic cells and mild fibrosis in bile duct system. Moderate to severe necrosis and fibrosis in hepatic cells and bile duct system appeared in the group of thirty times of administrations. 2. In the 25% ethyl alcohol administered group which was given five times of 2cc., the histopathological changes appeared for the first time in the form of mild focal necrosis in hepatic cells and mild fibrosis in bile duct system. The degree of histopathological changes of the hepatic cells and bile duct system generally was proportional to the number of drug administrations. The centrilobular necrosis was similar to carbon tetrachloride intoxication appeared in the subgroup of the ten times of administrations. 3. In the 50% ethyl alcohol administered group which was given two times of 2cc. , the histopathological changes appeared for the first time in the form of mild focal necrosis in hepatic cells and mild fibrosis in bile duct system. The tissue damage generally was proportional to the times of drug administraton. 4. In the 2:1 ethyl ether-ethyl alcohol administered group which was given two times of 2cc. , the histopathological changes appeared for the first time in the form of mild focal necrosis in hepatic cells and bile duct system. In this group diffuse hepatic cell necrosis, generally proportional to times of drug administrations, was more prominant than focal hepatic cell necrosis. 5. In the pure ethyl ether administered group, rabbits died from once or twice administration of ethyl ether 2cc with convulsive seizure. tachypnea, cardiac arrest. Ethyl ether was very toxic when it was infused through common bile duct in rabbits. Diffuse hemorrhagic necrosis in hepatic cells was shown with once or twice administration. 6. It is to be inferred that diluted ethyl alcohol, e.g. 25% ethyl alcohol solution, could several times be used for the purpose of removing the flukes in the bilary system.

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.

주파수특성을 고려한 직선배열 점음원에 의한 최적지향성합성

조기량,이정현 麗水水産大學校 産業技術硏究所 1995 産業基術硏究所 論文集 Vol.4 No.-

A numerical simulation is carried out on the optimal directivity synthesis considerated frequency character by point source array. Optimal algorithm DFP(Davidon Fletcher Powell) method is practiced by means of an iterative scheme. Desired directivity set for a beam width 21 degree and side lobe level-30dB. For the desired directivity, the directivity of the point source array considerating frequency approaches to iteration advances and the reasonable agreement is achived. Numerical simulations are carried out by using personal computer(CPU:80486DX2, RAM 16MByte).