• Title/Summary/Keyword: cytotoxin

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Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy

  • Hong, Beom-Ju;Kim, Jeongwoo;Jeong, Hoibin;Bok, Seoyeon;Kim, Young-Eun;Ahn, G-One
    • Radiation Oncology Journal
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    • v.34 no.4
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    • pp.239-249
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    • 2016
  • Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of 'reoxygenation' phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because 'reoxygenation' is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn't it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.

A Study on Anti-oxidative Activity of the Lithospermum Erythrorhizon Extracts for Application as a Cosmetic Ingredient

  • Park, Hee-Jeong;Lee, Ki-Young
    • Korean Journal of Plant Resources
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    • v.26 no.3
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    • pp.403-409
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    • 2013
  • This study has assessed the anti-oxidative activities and cytotoxic effects of Lithospermum erythrorhizon ethanol extract and measured the effects of tyrosinase inhibition activities with a goal of estimating the usage of the medicinal plant as an ingredient of cosmetics. First, to perform a basic test on the extract, pH and UV-spectrum were measured. According to the measurement, the extract had control functions at pH 5.5, and maximum absorbance occurred at 530nm. In particular, DPPH (1-1-diphenyl-2-picryl-hydrazyl)-inhibiting activity (IC50) and polyphenol content were 149.81 ${\mu}g/mL$ and $51.28{\pm}2.52$ mg/mL respectively. In addition, as extract concentration increased, tyrosinase inhibition activities improved as well. In raw 264.7 cell-based MTT assay, cell survival rates were 98% at 1000 ppm and 153% at 100 ppm. Therefore, it's been confirmed that there is almost no cytotoxin. According to the test results above, it appears that the Lithospermum erythrorhizon ethanol extract would be effective in anti-oxidation and application as a cosmetic ingredient.

Pathogenetic Impact of Vacuolar Degeneration by Accelerated Transport of Helicobacter pylori VacA

  • Choi, Kyung-Min;Park, Jeong-Kyu;Hwang, Se-Young
    • Journal of Microbiology and Biotechnology
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    • v.13 no.5
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    • pp.666-672
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    • 2003
  • Vacuolar degeneration of the gastric epithelial cells is a characteristic feature of the derangement of mucosa where Helicobacter pylori colonizes, and H. pylori vacuolating cytotoxin (VacA) has been suggested to playa key role in it. To elucidate the VacA-involved degenerative mechanism, VacA was purified, and its impact on degeneration of HeLa cells was determined. In the presence of ammonium chloride, cell vacuolation by VacA was dose-and time-dependent, however, no detectable degeneration of the cells was observed with the VacA concentration tested. A further increase of vacuolation was shown in cells pre-treated with diethyl pyrocarbonate (DEPC) , and this resulted in a change of the cell morphology to become spherical. Similar phenomena were also observed when HeLa cells were co-cultivated with intact H. pylori cells. It was remarkable to note that the degree of growth inhibition was proportional to the increase in vacuole formation, suggesting that the vacuolation rate would be critical for cell degeneration. Surprisingly, although VacA was itself inhibited by DEPC, its uptake was markedly increased by this agent, similar to that found in cells with Nabutyrate. These data indicate that the cell's tolerance of VacA transport may be critical for vacuolar degeneration and may be changeable during H. pylori inhabitation.

Characterization of Aeromonas hydrophila Isolated from Rainbow Trouts in Korea

  • Lee, Soondeuk;Kim, Sookyung;Yoojung Oh;Lee, Yeonhee
    • Journal of Microbiology
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    • v.38 no.1
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    • pp.1-7
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    • 2000
  • Eight strains of Aeromonas hydrophila isolated from diseased trout in Korea were characterized and compared with an American type strain by various methods including biochemical and physiological tests, PCR, randomly amplified polymorphic DNA (RAPD), plasmid profiling, and gel electrophoresis of total, membrane, and extracellular proteins. Virulence factors such as surface array proteins, cytotoxin, hemolysin, haemagglutinin, and protease were also investigated. The Korean strains showed heterogeneity in Iysine decarboxylase production, utilization of various carbon sources, and production of acetoin. Five strains had the same profiles of total and membrane proteins. Six strains haemagglutinated with trout red blood cells (RBCs) which was inhibited by fucose, galactose, and mannose, except for No. 1 where haemagglutination was inhibited by only galactose and mannose, but not by fucose. Four isolates haemagglutinated with human RBCs which was inhibited by fucose and mannose yet not by galactose. The type strain haemagglutinated only with trout RBCs which was inhibited by fucose, galactose, and mannose. Every isolate secreted protease, hemolysin, cytotoxin, and siderophore, but no enterotoxin. Results showed that the Korean isolates, except for No.7, had very different biochemical and molecular characteristics from those of the American type strain.

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Effect of Leweifang on HeLa Cell Vacuolation Induced by Helicobacter.pylori cytotoxin (Helicobacter pylori 독소에 의한 세포의 공포형성에 미치는 생약혼합물의 영향)

  • Kwon, Dong-Yeul;Cai, Gan;Shon, Yun-Hee;Nam, Kyung-Soo
    • Korean Journal of Pharmacognosy
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    • v.33 no.1 s.128
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    • pp.13-17
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    • 2002
  • Helicobacter pylori infection is associated with type B gastritis, peptic ulcer, and gastric cancer. The vacuolation of cells induced by H. pylori is thought to be essential for the initiation and maintenance of gastric infection. The roles of H. pylori cytotoxin, urease, and ammonia in the vacuolation of HeLa cells were determined. Ammonium chloride augmented the neutral red uptake induced by H. pylori toxin. Acetohydroxamic acid (AHA) failed to block the neutral red uptake induced by H. pylori toxin. Leweifang significantly prevented the vacuolation of HeLa cells induced by H. pylori toxin or H. pylori toxin and ammonium chloride. Further investigation is required to determine the mechanisms of Leweifang for the inhibition of vacuole formation of eukaryotic cells in response to the H. pylori toxin.

Antioxidant and Anticancer Effects of Water Extract from Pleurotus ostreatus (느타리버섯 물 추출물의 항산화 및 항암 활성 효과)

  • Choi, Hae Yeon;Ryu, Hye-Sook
    • The Korean Journal of Food And Nutrition
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    • v.28 no.1
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    • pp.60-65
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    • 2015
  • Mushrooms (Pleurotus ostreatus) have been used as traditional remedies as well as food sources. This study particularly used an extract of Pleurotus ostreatus among many other mushrooms for research to figure out the antioxidant activity and an effect of cytotoxin. The result of antioxidative effect was significantly increased at the high concentration. The otal contents of polyphenol and flavonoid were $30.2{\pm}0.7$ and $20.4{\pm}0.6$ respectively. Both reducing power and DPPH radical scavenging activities are highest at 5.0 mg/mL of concentration. According to the research about cytotoxin of normal cell, an extract of Pleurotus ostreatus showed no existence of toxicity based on 80.5% of viability. Meanwhile, Pleurotus ostreatus is not strongly effective on the growth of cancer cell, indicating anti-cancer effect has a quite high range of viability up to $70.0{\pm}5.3%$ in 5 mg/mL of concentration.

Pharmacodynamics of anticancer activity of tirapazamine and paclitaxel against human NSCLC

  • Park, Jong-Kook;Kang, Jin-Hyoung;Kuh, Hyo-Jeong
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.228.1-228.1
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    • 2002
  • Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Tirapazamine(TPZ). a hypoxia-selective cytotoxin. showed synergism with radiation or cytotoxic agents. Paclitaxel(PTX) is a highly active anti-cancer agent against Non small cell lung cancer(NSCLC), however. due to poor penetration into central hypoxic region of tumor tissue. combination with TPZ has been suggested to enhance its efficacy. (omitted)

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Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

  • Noh, Hye-Ji;Koh, Hong Bum;Kim, Hee-Kyoung;Cho, Hyang Hyun;Lee, Jeongmin
    • Nutrition Research and Practice
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    • v.11 no.1
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    • pp.11-16
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    • 2017
  • BACKGROUND/OBJECTIVES: Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS: The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), IL-$1{\beta}$, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS: G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-$1{\beta}$ and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION: G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention.