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Loss of the Retinoblastoma Gene in Non-Small Cell Lung Cancer (비소세포폐암에서의 망막모세포종유전자의 소실)

  • Lee, Choon-Taek;Kim, Chang-Min;Zo, Jae-Ill;Shim, Young-Mog;Hong, Weon-Seon;Lee, Jhin-Oh;Kang, Tae-Woong
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.2
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    • pp.98-103
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    • 1993
  • Background: Inactivation of retinoblastoma gene (Rb) has been observed in a variety of human cancers. Loss of heterozygosity (LOH) of Rb which is a common mode of allelic inactivation of Rb, has been known as a frequent genetic event in small cell lung cancer but it has been detected less frequently in non-small cell lung cancer. To define the role of Rb deletion in lung cancer, we investigated the genomic DNAs of 43 non-small cell lung cancers and 1 small cell lung cancer paired with normal lung tissues obtained by thoracotomy. Methods: The genomic DNAs were obtained by the digestion with proteinase K followed by phenol-chloroform extraction method. The genomic DNAs were digested by restriction endonuclease (EcoRI), separated by agarose gel electrophoresis, transferred to nylon membrane by Southern blot transfer and then hybridized with labelled Rb 1 probe which contains. 1.4 kb sized DNA sequence containing N-terminal portion of Rb. Results: In 26 squamous cell lung cancers, 16 cases were informative after EcoRI digestion and LOH of Rb was found in 10 cases (62.5%). In 17 adenocarcinomas of lung, 11 cases were informative and LOH of Rb was found in five cases (45.4%). The analysis of clinical parameters revealed no significant differences between the two groups with or without LOH of Rb in the aspects of age, sex, degree of differentiation, stage and smoking amount. Conclusions: These results suggest that Rb inactivation is also significantly involved in the molecular pathogenesis of non-small cell lung cancer.

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Expression of EGFR in Non-small Cell Lung Cancer and its Effects on Survival (비소세포 폐암에서 EGFR의 발현률과 생존률에 미치는 영향)

  • Kim, Hak-Ryul;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.6
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    • pp.1285-1295
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    • 1997
  • Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.

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Expression of Matrix Metalloproteinases-9 and Stromelysin-3 in Peripheral Blood in Patients with Lung Cancer (폐암 환자의 말초혈액에서 Matrix metalloproteinase-9 및 Stromelysin-3의 발현)

  • Lim, Seong-Yang;Koh, Won-Jung;Kim, Cheal-Hong;Ahn, Young-Mee;Kwon, Young-Mee;Kang, Kyeong-Woo;Kim, Ho-Cheal;Suh, Gee-Young;Chung, Man-Pya;Lim, Si-Young;Kim, Ho-Joong;Kwon, O-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.2
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    • pp.107-116
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    • 2002
  • Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.

Interleukin Levels in the Bronchoalveolar Lavage Fluid of Patients with Pulmonary Sarcoidosis (유육종증환자의 기관지폐포세척액내 Interleukin에 대한 연구)

  • Song, Jeong-Sup;Ahn, Joong-Hyun;Kim, Chi-Hong;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.1047-1057
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    • 1998
  • Background : Sarcoidosis is a systemic granulomatous disorder of unknown origin and characterized by accumulation of T cells and macrophages. Various cytokines may play crucial roles in the activation of T cells and macrophages, and thereby in the formation of granulomas. However, little is known about the balance between proinflammatory cytokines and antiinflammatory cytokines in the development of sarcoid granulomas and disease activities. In the present study, we measured IL-6, IL-8 and IL-10 in the bronchoalveolar lavage fluid(BALF) from patients with pulmonary sarcoidosis to find out whether there is an imbalance between proinflammatory cytokines and antiinflammatory cytokines in the lung. Methods: Fourteen subjects with the diagnosis of sarcoidosis and six healthy volunteers were included. BALF was concentrated ten-fold by pressure ultrafiltration and each cytokine levels were measured by EUSA method. Active sarcoidosis was defined by major organ involvement or clinically progressive diseases. Results: The mean IL-6 levels in the BALF of the active sarcoidosis group were significantly increased than in controls or inactive sarcoidosis group(p<0.05). Meanwhile, the IL-8 levels were increased and IL-10 levels were decreased in the active sarcoidosis group than in controls or inactive sarcoidosis group without significance(p>0.05). In active pulmonary sarcoidosis patients, the IL-6 levels in BALF correlated with the BALF CD4/CD8 ratio(r=0.768, p<0.05) and IL-8 levels(r=0.564, p<0.05). Conclusions : The data presented showed that pro-inflammatory cytokine IL-6 is important in the pathogenesis of sarcoidosis and decreased tendency of anti-inflammatory cytokine IL-10 might also be involved in the development of granulomatous inflammation in sarcoidosis.

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The Expression of MMPs and TIMPs in IPF and NSIP (IPF와 NSIP에서 MMPs와 TIMPs의 발현)

  • Kim, Yu Jin;Kim, Jung Ho;Jeon, Hyo Keun;Kim, Mi Kyeong;Jo, Young Chan;Kyung, Sun Yong;An, Chang Hyeok;Lee, Sang Pyo;Park, Jung Woong;Ha, Seung Yeon;Jeong, Sung Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.5
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    • pp.447-455
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    • 2006
  • Background: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. Method: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2, -9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. Results: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. Conclusions: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be important factors in the irreversible fibrosis of the lung parenchyme.

The effect of different crystallization temperature of the hydroxyapatite coating produced by ion beam-assisted deposition on anodizing-treated titanium disks on human osteosarcoma cells (양극산화처리된 티타늄 표면에 이온빔보조증착방식을 이용한 수산화인회석 코팅시 소결온도의 차이가 조골세포에 미치는 영향)

  • Pae, Ah-Ran;Won, Hyun-Du;Lee, Richard Sung-Bok;Kim, Hyeong-Seob;Woo, Yi-Hyung
    • The Journal of Korean Academy of Prosthodontics
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    • v.49 no.4
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    • pp.333-340
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    • 2011
  • Purpose: The aim of this study was to study the effect of hydroxyapatite (HA) coating crystallinity on the proliferation and differentiation of human osteosarcoma cells. Materials and methods: Surface roughness of the titanium disks increased by anodizing treatment and then HA was coated using ion beam-assisted deposition (IBAD). HA coating was crystallized by heat-treated at different temperature ($100^{\circ}C$, $300^{\circ}C$, $500^{\circ}C$, $800^{\circ}C$). According to the temperature, disks were divided into four groups (HA100, HA300, HA500, HA800). With the temperature, crystallinity of the HA coating was different. Anodized disks were used as control group. The physical properties of the disk surface were evaluated by surface roughness tests, XRD tests and SEM. The effect of the crystallinity of HA coating on HOS cells was studied in proliferation and differentiation. HOS cells were cultured on the disks and evaluated after 1, 3, 5, and 7 days. Growth and differentiation kinetics were subsequently investigated by evaluating cell proliferation and alkaline phosphatase activity. Results: Regardless of the heat-treated temperature, there is no difference on the surface roughness. Crystallinity of the HA was appeared in the groups of HA500, HA800. HOS cells proliferation, ALP activity were higher in HA500 and HA800 group than HA100 and HA300. Conclusion: Within the results of this limited study, heat treatment at $500^{\circ}C$ of HA coating produced by IBAD has shown greater effect on proliferation and differentiation of HOS cells. It is considered that further in vivo study will be necessary.

Reproductive Cycle of the Echiuroid Worm Urechis unicinctus(von Drasche) in Southern Korea (한국산 개불, Urechis unicinctus (von Drasche)의 생식주기)

  • 최상덕;김호진;이원교;곽은주;윤호섭;라성주;이인곤
    • Journal of Aquaculture
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    • v.13 no.2
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    • pp.169-174
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    • 2000
  • Reproductive cycle of U. unicinctus was studied from September 1998 to August 1999, using gonadosomatic index (CSI) as an indicator. In November, the CSI values were maximum for male (6.2) and female (7.0), respectively; the values were lowest for them (1.0 and 0.5) during the successive february. Subsequently, they rapidly increased and attained peak by March-April. The values decreased again in both sexes and remained unchanged until August. The index increased in October to attain the peak by November. The CSI values clearly indicated that there are two spawning events in a year, namely the first one during April-May and the second one in December. Reproductive cycle was classified into the following successive stages: in female, multipication (January~February, June ~Setember), maturation (March~April, November), spent (May and December), degeneration and resting (June and January), and in male, multiplication January ~ february, June ~September), maturation (March~April, October~November), spent (May and December) and degeneration and resting (January and June). Histological observations revealed that oocytes in the ovary matured simultaneously in November and March. At the same time, the envelopes of matured testis became thinner than those in the early stage.

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A Study on the Influence of Finishing and Polishing Methods on the Gap between Denture Base Resin and Soft Liner (의치의 마무리와 연마법이 의치상 레진과 연성 이장재 간의 공극에 미치는 영향에 관한 연구)

  • Jung, Seung-Hwan;Lee, Joon-Seok
    • Journal of Dental Rehabilitation and Applied Science
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    • v.24 no.4
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    • pp.325-335
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    • 2008
  • The junction between resilient denture liner and the denture base is difficult to finish and polish due to difference of the physical property of the materials. Gaps tend to be formed during finishing and polishing procedures. The purpose of this study was measuring the width of junctional gap between $Molloplast-B^{(R)}$ and denture base material after finishing and polishing procedure, and evaluating the effect of method and direction on gap width. $Molloplast-B^{(R)}$ was processed (according to the manufacturer's instruction) against Lucitone $199^{(R)}$ acrylic resin. 50 specimens were fabricated with a raised center section. All of specimens were examined and photographed with a stereoscopic microscope(x120), and the largest gap along the junction of $Molloplast-B^{(R)}$ and acrylic resin on each specimen was measured. One-way analysis of variance(ANOVA) and independent t-test at 95% confidence level were used to analyze the data and to compare groups. The results of this study were as follows. In comparison with finishing tools, the gap width was the largest in $Molloplast^{(R)}$-Cutter and the smallest in FSQ-cross cut bur. There was statistically significant difference between FSQ-cross cut bur and $Molloplast^{(R)}$-Cutter(p<0.05). There was no significant difference in gap width between the direction of polishing. The mean value of gap width was the smallest in case of no polishing, and the largest in case of polishing with pumice & tin oxide. There was statistically significant difference between pumice and pumice & tin oxide. From the results, it is concluded that the use of $Molloplast^{(R)}$-Cutter in clinic need serious consideration even though it has good cutting ability. Further careful study is needed for finishing and polishing methods for decreasing gap width in junction of two materials.

Role of HOXA Gene in Human Endometrial Decidualization (인간 자궁내막의 탈락막화에서 HOXA10 유전자의 역할)

  • Lee, Chang-Se;Park, Dong-Wook;Park, Chan-Woo;Kim, Tae-Jin
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.3
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    • pp.207-216
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    • 2010
  • Objective: This study was performed to clarify the role of HomeoboxA (HOXA) and its related signaling molecules in the decidualization of primary cultured endometrial cells. Methods: Human endometrial tissues were obtained by curettage of hysterectomy specimens from patients with conditions other than endometrial diseases. Tissues were minced and digested with Trypsin-EDTA for 20 min, $37^{\circ}C$. Cells were cultured with DMEM/F12 medium in $37^{\circ}C$, 5% $CO_2$ incubator for 24 hrs. Cells were treated with HOXA10 siRNA and added transforming growth factor (TGF)-${\beta}1$ (10 ng/mL) for 48 hrs to induces decidualization in vitro. Reverse transcription polymerase chain reaction analysis was accomplished to observe the expression of HOXA10, prolactin, cyclooxygenase (COX)-2, peroxisome proliferatoractivated receptor (PPAR)-$\gamma$, and wingless-type MMTV integration site family (Wnt). Results: HOXA10 expression was increased (1.8 fold vs. non-treated control) in TGF-${\beta}1$ treated cells. Decidualization marker, prolactin, was significantly increased in TGF-${\beta}1$ treated cells compared with HOXA10 siRNA treated cells. Endometrial cell differentiation marker, COX-2 was down-regulated by HOXA10 siRNA even if cells were treated with TGF-${\beta}1$. Wnt4 was down-regulated by treated with HOXA10 siRNA, this expression patters was not changed by TGF-${\beta}1$. Expression of PPAR-$\gamma$ was down regulated by TGF-${\beta}1$ in regardless of HOXA10 siRNA treatment. Conclusion: TGF-${\beta}1$ which is induced by progesterone in endometrial epithelial cells may induces stromal cell decidualization via HOXA10 and Wnt signaling cascade.

Antioxidative Activities and Antiaging Effects of Geum aleppicum Jacq. Extracts (큰뱀무 추출물의 항산화 활성 및 항노화에 관한 연구)

  • Kim, Min-Ji;Yang, Hyun-Gab;Park, Soo-Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.37 no.2
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    • pp.191-198
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    • 2011
  • In this study, antioxidative effects and inhibitory effects of Geum aleppicum Jacq. extracts on tyrosinase and elastase were investigated. The ethyl acetate fraction of G. aleppicum Jacq. extract ($4.70\;{\mu}g$/mL) showed the most prominent free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity (FSC50). Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of some G. aleppicum Jacq. extracts on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The ethyl acetate fraction showed the most prominent ROS scavenging activity ($0.22 \;{\mu}g$/mL). The protective effects of extract/fraction of G. aleppicum Jacq. against the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The G. aleppicum Jacq. extracts suppressed photohemolysis in a concentration dependent manner ($1{\sim}25{\mu}g$/mL), particularly the ethyl acetate fraction exhibited the most prominent celluar protective effect (${\tau}_{50}$, 416.20 min at $10 \;{\mu}g$/mL). The inhibitory effect of G. aleppicum Jacq. extracts on tyrosinase and elastase were investigated to assess their whitening and anti-winkle efficacy. The half maximal inhibitory concentration ($IC_{50}$) of the ethyl acetate fraction on tyrosinase was $95.23\;{\mu}g$/mL. The $IC_{50}$ of 50 % ethanol extract and the ethyl acetate fraction on elastase were $6.27 \;{\mu}g$/mL and $4.31 \;{\mu}g$/mL, respectively. These results indicate that extract/fraction of G. aleppicum Jacq. can function as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging $^1O_2$ and other ROS, and protect cellular membranes against ROS. Especially the ethyl acetate fraction of G. aleppicum Jacq. extracts could be applicable to new functional cosmetics for antioxidant, antiaging.