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Outcome of Limited Resection for Lung Cancer

  • Cho, Jeong-Su;Jheon, Sang-Hoon;Park, Sung-Joon;Sung, Sook-Whan;Lee, Choon-Taek
    • Journal of Chest Surgery
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    • v.44 no.1
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    • pp.51-57
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    • 2011
  • Background: Up to now, lobectomy, bilobectomy and pneumonectomy combined with extensive lymph node dissection have been regarded as the standard procedures for non-small cell lung cancer (NSCLC). In high-risk patients, however, limited resection (LR) has been attempted as a salvage procedure, and, recently, indication for LR has been extended to selected cases with early-stage NSCLC. Material and Methods: Among the 773 patients who underwent surgical procedures for NSCLC in Seoul National University Bundang Hospital from May 2003 to December 2008, 43 patients received LR. Medical records of these patients were retrospectively reviewed. Results: Mean age at operation was $66.0{\pm}12.4$ years, and there were 30 males. Twenty-five patients underwent conservative limited resection (CLR) and 18 underwent intentional limited resection (ILR). Indications for CLR were multiple primary lung cancer in 9 (9/25, 36%) and severe concomitant diseases in 5 (5/25, 20%). Of these, 6 patients underwent segmentectomy and 19 received wedge resection. During the follow-up period of $28.0{\pm}17.8$ months, 15 patient developed recurrent lung cancer. ILR was selectively performed in lesions almost purely composed of ground glass opacity (${\geq}$95%), or in small solid lesions (${\leq}$2 cm). Of these, 11 patients underwent segmentectomy and 7 underwent wedge resection. During the follow-up period of $31.7{\pm}11.6$ months, no patient developed recurrence. Conclusion: Intermediate-term outcome of LR for early-stage lung cancer is comparable to that of standard operation. For the delineation of the indications and appropriate surgical techniques for LR, prospective randomized multi-institutional study may be expedient.

Effect of Inorganic Particles on Organic Fouling in Pressurized Membrane Filtration (가압식 분리막 여과에서 무기입자의 존재가 유기파울링에 미치는 영향)

  • Jang, Hoseok;Kim, Jeonghwan
    • Membrane Journal
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    • v.30 no.2
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    • pp.131-137
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    • 2020
  • In this study, effect of inorganic particles on organic fouling was investigated by a laboratory-scaled pressurized membrane filtration. In order to cause organic fouling, sodium alginate (SA) was used as a feed solution. Regardless of the presence of inorganic SiO2 particles, the complete pore blocking played an important role in determining the fouling rate during the initial period of membrane filtration. However, the formation of cake layer resulted in the membrane fouling more dominantly as filtration time progressed. In the presence of inorganic particles, both specific cake resistance and compressibility associated with the membrane fouling formed were relatively lower than that without SiO2 particles. Membrane fouling was more severe at constant flux mode of filtration than that observed at constant pressure mode probably due to the concomitant increase of compressibility of fouling layer with transmembrane pressure (TMP). It was found that the presence of SA and SiO2 particles in feed solution provided the synergistic effect on the hydraulic backwashing to reduce membrane fouling as compared to the SA solution alone without the inorganic particles.

Induction of Apoptotic Cell Death by Methanol Extract of Houttuynia cordata Thunb. in A549 Human Lung Carcinoma Cells (어성초 메탄올 추출물에 의한 A549 인체 폐암세포 사멸유도에 관한 연구)

  • Hong, Su-Hyun;Park, Cheol;Hong, Sang-Hoon;Choi, Byung-Tae;Lee, Yong-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1584-1592
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    • 2006
  • Houttuynia cordata Thunb, well known as 'E-Sung-Cho' in Korea, is traditional medicinal plant generally used in Oriental medicine therapy. We previously reported that the water extract of H. cordata inhibited cell proliferation and induced apoptosis in human breast carcinoma cells. In the present study, we investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of H. cordata (MEHC) in human lung carcinoma A549 cells. It was found that MEHC could inhibit the cell growth in a dose-dependent manner, which was associated with morphological change and apoptotic cell death as determined by formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase cells. Apoptosis of A549 cells by MEHC was also connected with a down-regulation of anti-apoptotic Bcl-2 and inhibitor of apoptosis proteins (IAPs) expression. MEHC treatment induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant inhibition of poly(ADP-ribose) polymerase (PARP), ${\beta}$-catenin and phospholipase (PLC)-${\gamma}$1 protein expression. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. cordata.

Comparison Between TCDD and 3MC Action on CYP1A1 Expression and EROD Activity in the Isolated Perfused Female Rat Liver

  • Ahn, Mee R.;Sheen, Yhun Y.
    • Toxicological Research
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    • v.14 no.4
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    • pp.587-594
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    • 1998
  • In order to understand the mechanism if the regulation of CYP 1A1 gene expression and ethoxyresorufin deethylase (EROD) activity in ex vivo system, we have studied the action of TCDD and 3MC in the isolated perfused female rat liver. CYP1A1 mRNA level and EROD activity were measured in rat liver that was isolated and perfused with various chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), 17$\beta$-estradiol (E$_2$), morin. TCDD or 3MC alone perfusion into female rat liver resulted in increase of CYP 1A1 mRNA level and the magnitude of stimulation was six times higher with TCDD treatment than 3MC treatment. However E$_2$ perfusion into female rat liver showed inhibition of CYP 1A1 mRNA level. When 10$^{-8}$ M E$_2$ was administered concomitantly with either 10$^{-9}$ M TCDD or 10$^{-9}$ M 3MC, stimulated CYP 1A1 mRNA by either TCDD or 3MC was inhibited. Morin was examined for its effects on CYP 1A1 mRNA level and result was similar to that was observed with estrogen. EROD activity was also stimulated with either TCDD or 3MC perfusion, and the magnitude of EROD stiumlation was smaller than that of CYP 1A1 mRNA stimulation in response to TCDD or 3MC perfusion. Unlike CYP1A1 mRNA level, stimulation of EROD activity was greater with 3MC than TCDD. Concomitant perfusion either E$_2$ or morin with TCDD or 3MC inhibited 3MC perfusion or TCDD perfusion stimulated EROD activity. These data suggested that TCDD and 3MC might act diffrently in terms of regulation of CYP 1A1 gene expression in rat liver.

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Study on the Inhibitory Effects of Diallyl Sulfide and/or Diallyl Disulfide in the Rat Hepntocarcinogenesis (Diallyl Sulfide와 Diallyl Disulfide에 의한 랫드의 간암발생 억제효과에 관한 연구)

  • 김배환;이영순
    • Biomolecules & Therapeutics
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    • v.3 no.4
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    • pp.279-287
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    • 1995
  • This study examined the anti-cancer effects of diallyl sulfide(DAS) and/or diallyl disulfide(DDS), major components of garlic oil, with the DEN-PH model in rats, by the numbers and areas per cm$^2$ of induced glutathion S-transferase placental form(GST-P) positive foci and silver-stained nucleolar organizer regions(Ag-NORs) counts per nuclei in liver as indicator. Sprague-Dawley(SD) rats were given the diethylnitrosamine(DEN, 200 mg/kg, i.p.) as initiator and 2 weeks later, in experiment 1, rats were treated with DAS(200 mg/kg, i.g.) and/or DDS(50 mg/kg, i.g.) for 6 weeks, respectively and concomitantly and also were given the same dose of DAS and/or DDS prior to DEN treatment for 2 weeks, and in experiment II, rats were treated with potential cancer promoter, 2-acetylaminofluorene (2-AAF, 20 mg/kg, i.g.). The DAS and/or DDS were treated prior to 2-AAF for 8 weeks, respectively and concomitantly. Then the anti-promoting effects of DAS and/or DDS were assessed. All rats were subjected to the two-thirds partial hepatectomy(PH) at week 3 and sacrificed at week 8. In experiment I, DAS and/or DDS treatment only prior to DEN showed inhibition of the development of GST-P positive foci. In experiment II, DAS and/or DDS treatment prior to 2-AAF promotion showed obvious inhibition of the development of GST-P positive foci in numbers and areas and AgNORs counts. In conclusion, We found DAS and/or DDS had the preventive effects on the hepatocarcinogenesis in rats and the concomitant treatment had some additive effects compared with the each treatment and AgNORs counts correlated well with the preneoplastic hepatic lesion.

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Src Family Kinase Inhibitor PP2 Induces LC3 Conversion in a Manner That is Uncoupled from Autophagy and Increases Apoptosis in Multidrug-Resistant Cells

  • Kim, Yun-Ki;Ahn, Jun-Ho;Lee, Mi-Chael
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.393-398
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    • 2012
  • Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

Nitric oxide modulates antioxidant defense and the methylglyoxal detoxification system and reduces salinity-induced damage of wheat seedlings

  • Hasanuzzaman, Mirza;Hossain, Mohammad Anwar;Fujita, Masayuki
    • Plant Biotechnology Reports
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    • v.5 no.4
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    • pp.353-365
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    • 2011
  • The present study investigates the possible regulatory role of exogenous nitric oxide (NO) in antioxidant defense and methylglyoxal (MG) detoxification systems of wheat seedlings exposed to salt stress (150 and 300 mM NaCl, 4 days). Seedlings were pre-treated for 24 h with 1 mM sodium nitroprusside, a NO donor, and then subjected to salt stress. The ascorbate (AsA) content decreased significantly with increased salt stress. The amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) and the GSH/GSSG ratio increased with an increase in the level of salt stress. The glutathione S-transferase (GST) activity increased significantly with severe salt stress (300 mM). The ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), catalase (CAT) and glutathione peroxidase (GPX) activities did not show significant changes in response to salt stress. The glutathione reductase (GR), glyoxalase I (Gly I), and glyoxalase II (Gly II) activities decreased upon the imposition of salt stress, especially at 300 mM NaCl, with a concomitant increase in the $H_2O_2$ and lipid peroxidation levels. Exogenous NO pretreatment of the seedlings had little influence on the nonenzymatic and enzymatic components compared to the seedlings of the untreated control. Further investigation revealed that NO pre-treatment had a synergistic effect; that is, the pre-treatment increased the AsA and GSH content and the GSH/GSSG ratio, as well as the activities of MDHAR, DHAR, GR, GST, GPX, Gly I, and Gly II in most of the seedlings subjected to salt stress. These results suggest that the exogenous application of NO rendered the plants more tolerant to salinity-induced oxidative damage by enhancing their antioxidant defense and MG detoxification systems.

Activation of Small GTPases RhoA and Rac1 Is Required for Avian Reovirus p10-induced Syncytium Formation

  • Liu, Hung-Jen;Lin, Ping-Yuan;Wang, Ling-Rung;Hsu, Hsue-Yin;Liao, Ming-Huei;Shih, Wen-Ling
    • Molecules and Cells
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    • v.26 no.4
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    • pp.396-403
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    • 2008
  • The first ORF of the ARV S1133 S1 segment encodes the nonstructural protein p10, which is responsible for the induction of cell syncytium formation. However, p10-dependent signaling during syncytium formation is fully unknown. Here, we show that dominant negative RhoA, Rho inhibitor C3 exoenzyme, ROCK/Rho-kinase inhibitor Y-27632 and Rac1 inhibitor NSC23766 inhibit p10-mediated cell fusion. p10 over-expression is concomitant with activation and membrane translocation of RhoA and Rac1, but not cdc42. RhoA and Rac1 downstream events, including JNK phosphorylation and transcription factor AP-1 and $NF-{\kappa}B$ activation, as well as MLC expression and phosphorylation are simultaneously activated by p10. p10 point mutant T13M possessed 20% fusion-inducing ability and four p10 fusion-deficient mutants V15M, V19M, C21S and L32A reduced or lost their ability to activate RhoA and Rac1 signaling. We conclude that p10-mediated syncytium formation proceeds by utilizing RhoA and Rac1-dependent signaling.

Effects of Heat Treatment Conditions on Microstructure and Corrosion Resistance of Cu-contained Zr-Nb Alloy (Cu 첨가된 Zr-Nb계 합금에서 열처리조건이 미세조직과 내식성에 미치는 영향)

  • Choi, Byung Kwon;Baek, Jong Hyuk;Jeong, Yong Hwan
    • Journal of the Korean Society for Heat Treatment
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    • v.17 no.4
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    • pp.223-229
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    • 2004
  • The effects of the cooling and annealing conditions on the microstructures and corrosion properties were investigated for the Cu-contained Zr-Nb alloy (Zr-1.1Nb-0.07Cu). After annealing at $1050^{\circ}C$ for 15 min, the specimens were cooled by three methods of water quenching, air cooling, and furnace cooling. Widmanstatten structures were developed in both air- and furnace-cooled specimens, and the Widmanstatten plate width of the furnace-cooled specimens was wider than that of the air-cooled ones. The weight gain in the furnace-cooling case was higher than that in the air-cooling case. This could be the reason why the diffusion time was more enough during the furnace cooling than the air cooling. The oxide of the furnace-cooled specimen was nonunformly formed just beneath the Widmanstatten plate boundaries, where ${\beta}_{Zr}$ phases were exised concentrately. Compared with the $640^{\circ}C$ annealing after the water quenching, the $570^{\circ}C$ annealing could make the ${\beta}_{Nb}$ phases and a concomitant reduction of the Nb in the matrix, and then it could improve the corrosion resistance with the increase of the annealing time. It would be concluded that the corrosion resistance of the Zr-1.1Nb-0.07Cu was good when the Nb concentration in the matrix was reached at an equilibrium level and then the ${\beta}_{Nb}$ phase was formed.

Effects of Folio Acid Supplementation on Plasma Homocysteine and Thiobarbituric Acid Reactive Substances (TBARS) Levels and Liver SAM/SAH Ratio in Hyperhomocysteinaemia-induced Pregnant Rats (고호모시스테인혈증 임신 흰쥐에서 엽산보충이 혈장 호모시스테인, Thiobarbituric Acid Reactive Substances (TBARS) 수준과 간의 SAM/SAH에 미치는 영향)

  • Hong, Kyounk-Ju;Hyun, Tai-Sun;Chank, Nam-Soo
    • Journal of Nutrition and Health
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    • v.38 no.7
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    • pp.495-502
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    • 2005
  • This study was performed to investigate effects of dietary folic acid supplementation on plasma homocysteine levels, thiobarbituric acid reactive substance s (TBARS) level s and liver SAM/SAH ratio in hyperhomocysteinaemia-induced pregnant rats. Forty-two female Sprague-Dawley rats were divided three groups (C: control diet, HFD: $0.3\%$ homocystine and 0 mg folic acid diet, HFS: $0.3\%$ homocystine and 8 mg/kg folic acid diet) according to homocystine and folic acid levels in the diet. They were fed experimental diets for 5 weeks prior to the mating and also during the entire period of pregnancy till gestational day 20. Dietary folic acid supplementation caused a significant decrease in plasma homocysteine levels which had been increased by a homocystine-diet, with a concomitant increase in plasma and liver folate levels. Liver TBARS levels in homocysteine-folic acid-deficient group (HFD) were higher than those in control group. Dietary folic acid supplementation increased hepatic SAM/SAM ratio in homocysteine-folic acid- sopplemetantion group (HFS) when compared to the HFD (p < 0.05). These data suggest that folate depletion and elevated plasma homocysteine may promote oxidative stress in rat livers and influence the remethylation cycle of the homocysteine metabolism detrimentally. In conclusion, dietary folic acid supplementation was found to be effective for lowering plasma homocysteine levels, relieving oxidative stress, and improving the methylation status in the body.