• Title/Summary/Keyword: Growth-inhibitor

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Studies on Sclerotium rolfsii Sacc. isolated from Magnolia kobus DC. in Korea (목련(Magnolia kobus DC.)에서 분리한 흰비단병균(Sclerotium rolfsii Sacc.)에 관한 연구)

  • Kim Kichung
    • Korean journal of applied entomology
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    • v.13 no.3 s.20
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    • pp.105-133
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    • 1974
  • The present study is an attempt to solve the basic problems involved in the control of the Sclerotium disease. The biologic stranis of Sclerotium rolfsii Sacc., pathogen of Sclerotium disease of Magnolia kobus, were differentiated, and the effects of vitamins, various nitrogen and carbon sources on its mycelial growth and sclerotial production have been investigated. In addition the relationship between the cultural filtrate of Penicillium sp. and the growth of Sclerotium rolfsii, the tolerance of its mycelia or sclerotia to moist heat or drought and to Benlate (methyl-(butylcarbamoy 1)-2-benzimidazole carbamate), Tachigaren (3-hydroxy-5-methylisoxazole) and other chemicals were also clarified. The results are summarizee as follows: 1. There were two biologic strains, Type-l and Type-2 among isolates. They differed from each other in the mode of growth and colonial appearance on the media, aversion phenomenon and in their pathogenicity. These two types had similar pathogenicity to the Magnolia kobus and Robinia pseudoacasia, but behaved somewhat differently to the soybaen and cucumber, the Type-l being more virulent. 2. Except potassium nitrite, sodium nitrite and glycine, all of the 12 nitrogen sources tested were utilized for the mycelial growth and sclerotial production of this fungus when 10r/l of thiamine hydrochloride was added in the culture solution. Considering the forms of nitrogen, ammonium nitrogen was more available than nitrate nitrogen for the growth of mycelia, but nitrate nitrogen was better for sclerotia formation. Organic nitrogen showed different availabilities according to compounds used. While nitrite nitrogen was unavailable for both mycelial growth and sclerotial formation whether thiamine hydrochlioride was added or not. 3. Seven kinds of carbon sources examined were not effective in general, as long as thiamine hydrochloride was not added. When thiamine hydrochloride was added, glucose and saccharose exhibited mycelial growth, while rnaltose and soluble starch gave lesser, and xylose, lactose, and glycine showed no effect at all,. In the sclerotial production, all the tested carbon sources, except lactose, were effective, and glucose, maltose, saccharose, and soluble starch gave better results. 4. At the same level of nitrogen, the amount of mycelial growth increased as more carbon Sources were applied but decreased with the increase of nitrogen above 0.5g/1. The amount of sclerotial production decreased wi th the increase of carbon sources. 5. Sclerotium rolfsii was thiamine-defficient and required thiamine 20r/l for maximun growth of mycelia. At a higher concentration of more than 20r/l, however, mycelial growth decreased as the concentration increased, and was inhibited at l50r/l to such a degree of thiamine-free. 6. The effect of the nitrogen sources on the mycelial growth under the presence of thiamine were recognized in the decreasing order of $NH_4NO_3,\;(NH_4)_2SO_4,\;asparagine,\;KNO_3$, and their effects on the sclerotial production in the order of $KNO_3,\;NH_4NO_3,\;asparagine,\;(NH_4)_2SO_4$. The optimum concentration of thiamine was about 12r/l in $KNO_3$ and about 16r/l in asparagine for the growth of mycelia; about 8r/l in $KNO_3$ and $NH_4NO_3$, and 16r/l in asparagine for the production of sclerotia. 7. After the fungus started to grow, the pH value of cultural filtrate rapidly dropped to about 3.5. Hereafter, its rate slowed down as the growth amount increased and did not depreciated below pH2.2. 8. The role of thiamine in the growth of the organism was vital. If thiamine was not added, the combination of biotin, pyridoxine, and inositol did not show any effects on the growth of the organism at all. Equivalent or better mycelial growth was recognized in the combination of thiamine+pyridoxine, thiamine+inositol, thiamine+biotin+pyridoxine, and thiamine+biotin+pyridoxine+inositol, as compared with thiamine alone. In the combinations of thiamine+biotin and thiamine+biotin+inositol, mycelial growth was inhibited. Sclerotial production in dry weight increased more in these combinations than in the medium of thiamine alone. 9. The stimulating effects of the Penicillium cultural filtrate on the mycelial growth was noticed. It increased linearly with the increase of filtrate concentration up to 6-15 ml/50ml basal medium solution. 10. $NH_4NO_3$. as a nitrogen source for mycelial growth was more effective than asparasine regardless of the concentration of cultural filtrate. 11. In the series of fractionations of the cultural filtrate, mycelial growth occured in unvolatile, ether insoluble cation-adsorbed or anion-unadsorbed substance fractions among the fractions of volatile, unvolatile acids, ether soluble organic acids, ether insoluble, cation-adsorbed, cation-unadsorbed, anion-adsorbed and anion-unadsorbed. and anion-un-adsorbed substance tested. Sclerotia were produced only in cation-adsorbed fraction. 12. According to the above results, it was assumed that substances for the mycelial growth and sclerotial formation and inhibitor of sclerotial formation were include::! in cultural filtrate and they were quite different from each other. I was further assumed that the former two substances are un volatile, ether insotuble, and adsorbed to cation-exchange resin, but not adsorbed to anion, whereas the latter is unvolatile, ether insoluble, and not adsorbed to cation or anion-exchange resin. 13. Seven amino acids-aspartic acid, cystine, glysine, histidine, Iycine, tyrosine and dinitroaniline-were detected in the fractions adsorbed to cation-exchange resin by applying the paper chromatography improved with DNP-amino acids. 14. Mycelial growth or sclerotial production was not stimulated significantly by separate or combined application of glutamic acid, aspartic acid, cystine, histidine, and glysine. Tyrosine gave the stimulating effect when applied .alone and when combined with other amino acids in some cases. 15. The tolerance of sclerotia to moist heat varied according to their water content, that was, the dried sclerotia are more tolerant than wet ones. The sclerotia harvested directly from the media, both Type-1 and Type-2, lost viability within 5 minutes at $52^{\circ}C$. Sclerotia dried for 155 days at$26^{\circ}C$ had more tolerance: sclerotia of Type-l were killed in 15 mins. at $52^{\circ}C$ and in 5 mins. at $57^{\circ}C$, and sclerotia of Type-2 were killed in 10 mins. both at $52^{\circ}C$ or $57^{\circ}C$. 16. Cultural sclerotia of both strains maintained good germinability for 132 days at$26^{\circ}C$. Natural sclerotia of them stored for 283 days under air dry condition still had good germinability, even for 443 days: type-l and type-2 maintained $20\%$ and $26.9\%$ germinability, respectively. 17. The tolerance to low temperature increased in the order of mycelia, felts and sclerotia. Mycelia completely lost the ability to grow within 1 week at $7-8^{\circ}C$> below zero, while mycelial felts still maintained the viability after .3 weeks at $7-20^{\circ}C$ below zero, and sclerotia were even more tolerant. 18. Sclerotia of type-l and type-2 were killed when dipped into the $0.05\%$ solution of mercury chloride for 180 mins. and 240 mins. respectively: and in the $0.1\%$ solution, Type-l for 60 mins. and Type-2 for 30 mins. In the $0.125\%$ uspulun solution, Type-l sclerotia were killed in 180 mins., and those of Type-2 were killed for 90 mins. in the$0.125\%$solution. Dipping into the $5\%$ copper sulphate solution or $0.2\%$ solution of Ceresan lime or Mercron for 240 mins. failed to kill sclerotia of either Type-l or Type-2. 19. Inhibitory effect on mycelial growth of Benlate or Tachi-garen in the liquid culture increased as the concentration increased. 6 days after application, obvious inhibitory effects were found in all treatments except Benlate 0.5ppm; but after 12 days, distingushed diflerences were shown among the different concentrations. As compared with the control, mycelial growth was inhibited by $66\%$ at 0.5ppm and by $92\%$ at 2.0ppm of Benlate, and by$54\%$ at 1ppm and about $77\%$ at 1.5ppm or 2.0ppm of Tachigaren. The mycelial growth was inhibited completely at 500ppm of both fungicides, and the formation of sclerotia was checked at 1,000ppm of Benlate ant at 500ppm or 1,000ppm of Tachigaren. 20. Consumptions of glucose or ammonium nitrogen in the culture solution usually increased with the increment of mycelial growth, but when Benlate or Tachigaren were applied, consumptions of glucose or ammonium nitrogen were inhibited with the increment of concentration of the fungicides. At the low concentrations of Benlate (0.5ppm or 1ppm), however, ammonium nitrogen consumption was higher than that of the ontrol. 21. The amount of mycelia produced by consuming 1mg of glucose or ammonium nitrogen in the culture solution was lowered markedly by Benlate or Tachigaren. Such effects were the severest on the third day after their treatment in all concentrations, and then gradually recovered with the progress of time. 22. In the sand culture, mycelial growth was not inhibited. It was indirectly estimated by the amount of $CO_2$ evolved at any concentrations, except in the Tachigaren 100mg/g sand in which mycelial growth was inhibited significantly. Sclerotial production was completely depressed in the 10mg/g sand of Benlate or Tachigaren. 23. There was no visible inhibitory effect on the germination of sclerotia when the sclerotia were dipped in the solution 0.1, 1.0, 100, 1.000ppm of Benlate or Tachigaren for 10 minutes or even 20 minutes.

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A Study on the Conversion to Feed Stuff from Cellulosic Biomass (섬유질자원(纖維質資源)의 사료(飼料) 전환(轉換))

  • Lee, Ke-Ho;Sung, Chang-Geun;Chung, Kyu-Ok
    • Applied Biological Chemistry
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    • v.27
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    • pp.29-46
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    • 1984
  • To utilize several species of hard wood as raw materials of feed products, fermentation characteristics of cellulosic substrates to single cell protein was investigated, and results were summarized as follows. Among the microorganisms investigated, Tricoderma viride was selected as one of the most cellulolytic. Mixed culture of fungi did not show a synergistic effect on cellulose degradation. When the fungi were cultured at $28^{\circ}C$ for 7 days in a medium containing wheat bran 25 g, cellulose 0.25 g, proteose peptone 0.025 g and tween 800.025 g, cellulotic activities on carboxy methyl cellulose and filter paper reached maximum at 12 hr. The alkali treatment resulted in increased degradation of substrate from 13 to 18% when treated with enzymes for 12h, and reducing sugar formation increased with decreased size of substrates. Glucose was a very good feedback inhibitor of the enzyme from T.viride than that of xylose. When the substrate was rehydrolyzed, hydrolysis rate was 31% to reducing sugars within 12 hr. Quantative anlysis with HPLC showed the ratio of glucose to xylose in sugar syrups as 1.77 to 1. For the purpose of producing cellulosic-single cell protein from the sawdust of mulberry tree, 15 strains of xylose-assimilating yeast were isolated from 42 samples of rotten woods and compost soils and examined for their ability to utilize xylose. Then three strains were selected by their strong xylose-assimilating activities. The cultivative condition, the growth characteristics, and protein and nucleic acid productivities of three strains were investigated. The results obtained were, 1. Wood hydrolysate of mulberry tree was assimilated by 5 strains of CHS-2, CHS-3, ST-40, CHS-12 and CHS-13. 2. The optimum initial pH and temperature for the growth of strain CHS-13 were 4.4 and $30^{\circ}C$. 3. The specific growth rate of strain CHS-13 was $0.23h^{-1}$ and generation time was 3.01 hrs at the optimum condition. 4. CHS-13 strain assimilated 81 % of sugar in wood hydrolysate. 5. CHS-13 strain was identified as Candida guilliermondii var. guilliermondii 6. When the CHS-13 strain was cultured in the wood hydrolysate containing yeast extract, L-protein content was increased with yeast extract concentration. 7. The L-protein and nucleic acid yields from wood hydrolysate were 0.73 mg/ml and $4.92{\times}10^{-2}\;mg/ml$ respectively. 8. An optimal nucleic acid content of CHS-13 strain was observed in the medium containing 0.2% of yeast extract.

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The Role of Uteroglobin in the Immunomodulation of Nonsmall Cell Lung Cancer Cells (비소세포 폐암세포에서 Uteroglobin의 면역 조절 기능에 대한 연구)

  • Yoon, Jung Min;Lim, Jae-Jun;Yoo, Chul-Gyu;Lee, Choon-Taek;Han, Sung Koo;Shim, Young-Soo;Kim, Young Whan
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.4
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    • pp.336-344
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    • 2004
  • Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

Effects of Regular Exercise and L-Arginine Intake on Abdominal Fat, GH/IGF-1 Axis, and Circulating Inflammatory Markers in the High Fat Diet-Induced Obese Aged Rat (규칙적인 운동과 L-arginine의 섭취가 고지방식이 유도 비만 노화생쥐의 복부지방량, GH/IGF-1 axis 및 혈관염증지표에 미치는 영향)

  • Park, Sok;Sung, Ki-Woon;Lee, Jin;Lee, Cheon-Ho;Lee, Young-Jun;Yoo, Young-June;Park, Kyoung-Shil;Min, Byung-Jin;Shin, Yong-Sub;Kim, Jung-Suk;Jung, Hun
    • Journal of Life Science
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    • v.22 no.4
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    • pp.516-523
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    • 2012
  • The purpose of this study was to investigate the effect of exercise and/or L-arginine on abdominal fat, IGF-1 on GH/IGF-1 axis, fibrinogen, and PAI-1 in aged and obese rats. Male Sprague-Dawley rats were treated with a D-galactose aging inducing agent (50 mg/kg) given intraperitoneally for 12 weeks. Thirty-two male Sprague-Dawley rats were treated and divided into four groups: aging-high fat diet group (AG+HF), AG+HF with L-arginine intake group (AG+LA), AG+HF with exercise group (AG+EX), and AG+EX with L-arginine intake group (AG+LA+EX). The experimental rats underwent treadmill training (60 min/day, 6 days/week at 0% gradient) for 12 weeks. L-arginine was given orally (150 mg/kg/day) for 12 weeks. After the experiment, blood was collected from the left ventricle and abdominal fat was extracted. The results showed that GH was significantly increased in AG+EX and AG+AL+EX. IGF-1 was significantly increased in both the AG+AL+EX and AG+EX group ($p$<0.05), while fibrinogen and PAI-1 were not significantly different among the groups. Abdominal fat was significantly decreased in the AG+LA, AG+EX, and AG+LA+EX groups ($p$<0.05) compared with the AG+HF group. In conclusion, this study suggests that exercise alone or L-arginine alone or a combination not only increases the GH and IGF-1 concentration, but also decreases the abdominal fat mass.

Forsythiae Fructus Induces VEGF Production via p38 MAPK Activation in Human Keratinocytes (각질형성세포에서 p38 MAPK 활성을 통한 연교의 VEGF 생성 효과)

  • Kim, Mi-Sun;Choi, Yun Ho;Park, Sun Gyoo;Lee, Cheon Koo;Lee, Sang Hwa
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.4
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    • pp.329-336
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    • 2016
  • Cutaneous microvasculature plays a critical role in age-associated skin changes. A considerable reduction of number and size of vessels has been observed in the upper dermis of elderly skin. Forsythiae fructus (FF), the dried fruit of plant Forsythia suspensa (F. suspensa), has been traditionally used as an herbal medicine to treat inflammatory diseases and bacterial diseases. However, its regulatory effect on angiogenic responses has not been elucidated in skin. Therefore, we analyzed secretory profiles upon treatment of FF extract using array designed to detect angiogenesis-associated mediators in human keratinocytes. Because keratinocyte-derived VEGF (vascular endothelial growth factor) has been regarded as a potent factor for new microvasculature under the epidermis, we further investigated the effect of FF extract on VEGF production. We observed that the VEGF expression of mRNA and protein level was increased by about 2 folds in a dose-dependent manner after FF extract treatment. In signaling experiments, FF extract induced rapid p38 MAPK activation within 5 min, and the activation was totally abrogated by pretreatment with a p38 MAPK specific inhibitor. The FF-induced VEGF upregulation was also significantly attenuated by a p38 MAPK inhibition. Taken together, FF extract induces VEGF production via p38 MAPK activation in human epidermal keratinocytes. These novel findings suggest that FF is useful as a potential agent with pro-angiogenic activity and may help to improve age-dependent reduction of the microvasculature in aged skin or to heal skin wound.

Evaluation of Hydrate Inhibition Performance of Water-soluble Polymers using Torque Measurement and Differential Scanning Calorimeter (토크 측정과 시차주사열량계를 이용한 수용성 고분자 화합물의 하이드레이트 저해 성능 평가)

  • Shin, Kyuchul;Park, Juwoon;Kim, Jakyung;Kim, Hyunho;Lee, Yohan;Seo, Yongwon;Seo, Yutaek
    • Korean Chemical Engineering Research
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    • v.52 no.6
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    • pp.814-820
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    • 2014
  • In this work, hydrate inhibition performance of water-soluble polymers including pyrrolidone, caprolactam, acrylamide types were evaluated using torque measurement and high pressure differential scanning calorimeter (HP ${\mu}$-DSC). The obtained experimental results suggest that the studied polymers represent the kinetic hydrate inhibition (KHI) performance. 0.5 wt% polyvinylcaprolactam (PVCap) solution shows the hydrate onset time of 34.4 min and subcooling temperature of 15.9 K, which is better KHI performance than that of pure water - hydrate onset time of 12.3 min and subcooling temperature of 6.0 K. 0.5 wt% polyvinylpyrrolidone (PVP) solution shows the hydrate onset time of 27.6 min and the subcooling temperature of 13.2 K while polyacrylamide-co-acrylic acid partial sodium salt (PAM-co-AA) solution shows less KHI performance than PVP solution at both 0.5 and 5.0 wt%. However, PAM-co-AA solution shows slow growth rate and low hydrate amount than PVCap. In addition to hydrate onset and growth condition, torque change with time was investigated as one of KHI evaluation methods. 0.5 wt% PVCap solution shows the lowest average torque of 6.4 N cm and 0.5 wt% PAM-co-AA solution shows the average torque of 7.2 N cm. For 0.5 wt% PVP solution, it increases 11.5 N cm and 5.0 wt% PAM-co-AA solution shows the maximum average torque of 13.4 N cm, which is similar to the average torque of pure water, 15.2 N cm. Judging from the experimental results obtained by both an autoclave and a HP ${\mu}$-DSC, the PVCap solution shows the best performance among the KHIs in terms of delaying hydrate nucleation. From these results, it can be concluded that the torque change with time is useful to identify the flow ability of tested solution, and the further research on the inhibition of hydrate formation can be approached in various aspects using a HP ${\mu}$-DSC.

Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

  • Berk, Veli;Kaplan, Mehmet Ali;Tonyali, Onder;Buyukberber, Suleyman;Balakan, Ozan;Ozkan, Metin;Demirci, Umut;Ozturk, Turkan;Bilici, Ahmet;Tastekin, Didem;Ozdemir, Nuriye;Unal, Olcun Umit;Oflazoglu, Utku;Turkmen, Esma;Erdogan, Bulent;Uyeturk, Ummugul;Oksuzoglu, Berna;Cinkir, Havva Yesil;Yasar, Nurgul;Gumus, Mahmut
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7367-7369
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    • 2013
  • Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

The Efficacy of ZD1839 ($Iressa^{TM}$) in Patients with Advanced Non-small Cell Lung Cancer which has Progressed After Previous Chemotherapy (표준 항암화학요법에 실패한 진행성 비소세포폐암에서 ZD1839 ($Iressa^{TM}$)의 효과)

  • Lee, Seung Whan;Kim, Duck Ryung;Lee, Sang Dae;Lee, Jong Sin;Park, Yeon Hee;Ryoo, Baek-Yeol;Kim, Heung Tae;Park, Sunhoo;Kim, Bong Seog;Kim, Cheol Hyeon;Lee, Jae Cheol
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.2
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    • pp.160-168
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    • 2004
  • Background : The role of second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) is known to be limited. Recently, ZD1839, the small molecule epidermal growth factor receptor-tyrosine kinase inhibitor, has been developed and has shown anti-tumor activity in patients with solid malignant tumors including lung cancer. We evaluated the response rate and toxicities of ZD1839 in patients with advanced NSCLC which has progressed after previous chemotherapy. Patients and Methods : We examined 83 patients with advanced NSCLC treated with ZD1839 for more than 1 month in Korea Cancer Center Hospital during the period from January 2002 to September 2003. All the patients were enrolled in the international expanded access program (EAP) with ZD1839 by AstraZeneca. The administered dose of ZD1839 was 250 mg once daily. Chest radiography and laboratory tests were followed-up. We evaluated the response rate, median survival, and toxicity after treatment. Results : Median age of the patients was 59 years (range 33-76). The most predominant cell type was adenocarcinoma and the most stage of the patients was IV. ECOG performance status was as follows; grade 0-1 in 10, grade 2 in 42, and grade 3 in 31 patients. Partial response was achieved in 12 patients (14.5%). Median overall survival was 9.2 (range 1.3-21.6+) months and median time to progression was 3.1 (range 1-21.2+) months. The most common adverse effect of ZD1839 was skin eruption which developed in 25 patients (25.8%). Significantly higher response rate and survival was found in patients with adenocarcinoma or good performance status. Conclusion : ZD1839 showed modest activity and tolerable toxicity in the treatment for patients with NSCLC which has progressed after previous chemotherapy.

Induction of Apoptosis by Ethanol Extract of Lythrum anceps (Koehne) Makino in Human Leukemia U937 Cells (인체백혈병 U937 세포에서 부처꽃 에탄올추출물에 의한 apoptosis 유도)

  • Jeong, Jin-Woo;Kim, Chul Hwan;Lee, Young-Kyung;Hwang, Yong;Lee, Ki Won;Choi, Kyung-Min;Kim, Jung Il
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.279-286
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    • 2020
  • Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer effect are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins, depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

Inhibition of Cancer Cell Migration by Compounds from Garlic Extracts (마늘추출물에 의한 암세포의 이동 저하)

  • Kim, Eun-Kyoung;Yun, Sung-Ji;Ha, Jung-Min;Jin, In-Hye;Kim, Young-Whan;Kim, Sun-Gun;Park, Da-Jung;Choi, Young-Whan;Yun, Sik;Kim, Chi-Dae;Bae, Sun-Sik
    • Journal of Life Science
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    • v.21 no.6
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    • pp.767-774
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    • 2011
  • Cell migration plays a fundamental role in cancer cell invasion and metastasis as well as in many physiological responses. Here, we screened four different sources of garlic - water extract of normal and black garlic, as well as dried normal and black garlic - for the identification of anti-invasive and anti-metastatic activity on cancer cells. Inhibition of cancer cell migration was observed in the hexane extract of dried-garlic. Inhibitory activity was further purified to near homogeneity by thin layer chromatography and named $\b{i}$nhibitor of $\b{c}$ancer $\b{m}$etastasis from garlic #27 (ICMG-27). ICMG-27 completely blocked insulin-like growth factor-1 (IGF-1)-induced OVCAR-3 cell migration at 6 ${\mu}g/ml$. ICMG-27 completely blocked IGF-1-induced OVCAR-3 and NIH-3T3 cell migration whereas IGF-1-induced mouse embryonic fibroblast (MEF) cell migration was not affected byICMG-27. ICMG-27 inhibited all the tested IGF-1-induced cancer cell migration such as OVCAR-3, SKOV-3, and MDA-MB-231 cells. Finally, ICMG-27 could inhibit IGF-1-, lysophosphatidic acid (LPA)-, sphingosine-1-phosphate (S1P)-, leukotriene B4 (LTB4)-, and angiotensin II (AngII)-induced OVCAR-3 cell migration. These results indicate that ICMG-27 inhibits cancer cell migration by blocking essential steps in many agonists-induced cancer cell migrations. Unveiling an anti-invasive mechanism of ICMG-27 on cancer cells will provide a basis for cancer therapy.