• 제목/요약/키워드: Cytotoxic drug

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Isolation and Characterization of Two Korean Mistletoe Lectins

  • Kang, Tae-Bong;Song, Seong-Kyu;Yoon, Taek-Joon;Yoo, Yung-Choon;Lee, Kwan-Hee;Her, Erk;Kim, Jong-Bae
    • BMB Reports
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    • v.40 no.6
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    • pp.959-965
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    • 2007
  • Two isolectins (KML-IIU and the KML-IIL) were individually isolated from the previously reported Korean mistletoe lectin, KML-C, by using an immunoaffinity column. Molecular weights of the KML-IIU and the KML-IIL were 64 kDa and 60 kDa respectively. Both of the lectins were composed of heterogeneous A and B subunits linked with a disulfide bond, and showed the same carbohydrate-binding specificities for Gal and GalNAc. However, they are different not only in biophysical properties (glycosylation and amino acid compositions) but also bioactivities (cell killing and cytokine induction). The KML-IIL showed 17-145 times stronger in cytotoxicities to various human and mouse cancer cell lines than the KML-IIU. The KML-IIL also induced TNF-$\alpha$ secretion from mouse peritoneal macrophages 4.5 times better than the KML-IIU. The results demonstrated isolectins in Korean mistletoe were varied in bioactivities and the KML-IIL may be developed as an anti-cancer agent.

Complications of nephrotic syndrome

  • Park, Se-Jin;Shin, Jae-Il
    • Clinical and Experimental Pediatrics
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    • v.54 no.8
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    • pp.322-328
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    • 2011
  • Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox), thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia, bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS.

Adaptive Responses on Survival and Mutagenesis during MNNG Pretreatmeat and Lethality to UV MNNG at Different Cell Stages in Aspergillus nidulans (Aspergillus nidulans에서 MNNG 선 처리시의 생존도와 돌연변이 유발에 대한 Adaptive response 및 Cell stage 따른 UV와 MNNG에 대한 치사율 조사)

  • Chae, Suhn-Kee
    • The Journal of Natural Sciences
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    • v.9 no.1
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    • pp.45-52
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    • 1997
  • We have examined the effects of low concentrations of MNNG, alkylating agent, in survival and mutagenesis in Aspergillus nidulans. Pretreatments of cells with nontoxic and submutagenic doses of MNNG did not reduce the cytotoxic and mutagenic effects of exposure to a high concentration of drug. The results imply that adaptive responses on survival and mutagenesis for MNNG treatments do not occur in Aspergillus nidulans. In the first mitotic cell cycle during germination, the sensitivity to MNNG has been investigated at hourly time interval, and compared with that for UV irradiation. In both UV and MNNG treatments, the sensitivity increased till S cell stage, and decreased while DNA replication continued. Different from that show for UV irradiation, lethality to MNNG reached to the maximum at G2 cell stage.

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Determination of Mertansine in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry and Pharmacokinetics of Mertansine in Rats

  • Choi, Won-Gu;Kim, Ju-Hyun;Jang, Hyun-Joon;Lee, Hye Suk
    • Mass Spectrometry Letters
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    • v.11 no.3
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    • pp.59-64
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    • 2020
  • Mertansine, a thiol-containing maytansinoid, is a tubulin inhibitor used as the cytotoxic component of antibody-drug conjugates for the treatment of cancer. Liquid chromatography-tandem mass spectrometry was described for the determination of mertansine in rat plasma. 50-μL rat plasma sample was pretreated with 25 μL of 20 mM tris-(2-carboxyethyl)-phosphine, a reducing reagent, and further vortex-mixing with 50 μL of 50 mM N-ethylmaleimide for 3 min resulted in the alkylation of thiol group in mertansine. Alkylation reaction was stopped by addition of 100 μL of sildenafil in acetonitrile (200 ng/mL), and following centrifugation, aliquot of the supernatant was analyzed by the selected reaction monitoring mode. The standard curve was linear over the range of 1-1000 ng/mL in rat plasma with the lower limit of quantification level at 1 ng/mL. The intra- and inter-day accuracies and coefficient variations for mertansine at four quality control concentrations were 96.7-113.1% and 2.6-15.0%, respectively. Using this method, the pharmacokinetics of mertansine were evaluated after intravenous administration of mertansine at doses of 0.2, 0.5, and 1 mg/kg to female Sprague Dawley rats.

Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches

  • Bano, Nusrat;Najam, Rahila;Qazi, Faaiza;Mateen, Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1637-1641
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    • 2016
  • Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

Effects of Olibanum Extracts on Vascular Cell Adhesion Molecules Expression (유향 추출물이 혈관내피세포 부착단백질 발현에 미치는 영향)

  • Lee, Soong-In;Kwon, Kang-Beom;Han, Jong-Hyun;Ryu, Do-Gon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.3
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    • pp.445-450
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    • 2011
  • In order to validate the use of Olibanum as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effect of water-soluble extract of Olibanum (EO) on the expression of pro-inflammatory vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-${\alpha}$. The extract inhibited dose-dependently VCAM-1 expression without its cytotoxic effect on HUVECs, as measured by a flow cytometer using fluorescence-enhanced anti-VCAM-1 antibody, and significantly decreased mRNA levels of VCAM-1, as determined using reverse transcription polymerase chain reaction. These results suggest that Olibanum may have therapeutic potential in the control of endothelial disorders caused by inflammation.

Hepatoprotective Effect of Stamen Extracts of Mesua ferrea L. against Oxidative Stress induced by $CCl_4$ in Liver Slice Culture Model

  • Rajopadhye, Anagha A.;Upadhye, Anuradha S.
    • Natural Product Sciences
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    • v.18 no.2
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    • pp.76-82
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    • 2012
  • Stamens of Mesua ferrea L. are a well-known herbal drug used in Indian System of Traditional Medicine to treat various diseases. The claimed activity of this plant part is necessitated to investigate antioxidant and hepatoprotective activity. Authenticated plant sample was extracted with hexane, ethanol (EtOH) and water (aq.) using ASE 100 accelerated solvent extractor. Antioxidant activity was evaluated by means of different in vitro assays. Hepatoprotective effect was investigated on carbon tetrachloride induced oxidative stress in liver slice culture model. Cytotoxic marker lactate dehydrogenase (LDH) released in culture medium and the activity of lipid peroxidation along with antioxidant enzymes (AOEs) namely superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were estimated. Hexane and EtOH extracts were significantly inhibited DPPH, NO, SOD and $ABTS^+$ radical in dose dependent manner. The trade of phenol content was: aq. extract < hexane extract < EtOH extract. A significant correlation was shown by total phenol content and free radical scavenging activity of extracts. The culture system treated with hexane extract, EtOH extract or ascorbic acid exhibited significant depletion in LDH, lipid peroxidation, antioxidative enzymes SOD, CAT and GR. Hexane extract and EtOH extracts of stamen of M. ferrea protected liver slice culture cells by alleviating oxidative stress induced damage to liver cells.

Enhanced Sensitivity to Proteasome Inhibitor Bortezomib in Nrf2 Knockdown Ovarian Cancer Cells (Nrf2 영구 넉다운 난소암 세포주의 Proteasome 저해 항암제 Bortezomib에 대한 감수성 증가)

  • Lee, Sang-Hwan;Choi, Bo-Hyun;Kwak, Mi-Kyoung
    • YAKHAK HOEJI
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    • v.55 no.6
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    • pp.466-472
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    • 2011
  • NF-E2-related factor 2 (Nrf2), a master regulator of antioxidant genes in animals, has been associated with the resistance of cancer cells to several cytotoxic chemotherapeutics. Bortezomib, a reversible inhibitor of the 26S proteasome, is a novel class anti-cancer therapeutics approved for the treatment of refractory multiple myeloma. However, the molecular mechanism of drug-resistance remains elusive. In the present study, bortezomib sensitivity has been investigated in Nrf2 knockdown ovarian cancer cells. When Nrf2 expression is stably repressed using interfering RNA expression, bortezomib-induced apoptosis and cell death were significantly enhanced compared to nonspecific RNA control cells. Knockdown cells showed elevated expression in the catalytic subunit PSMB5, PSMB6, and PSMB7 compared to the control, and failed to induce heme oxygenase-1 expression following bortezomib treatment. These indicate that differential proteasome levels and altered expression of stress-response genes could be underlying mechanisms of bortezomib sensitization in Nrf2-inhibited ovarian cancer cells.

Selective Cytotoxicity of New Platinum (II) Complex Containing 1,2-Diaminopropane (1,2-디아미노프로판을 배위자로 한 백금(II) 착체의 선택적 세포독성)

  • Rho, Young-Soo;Lee, Kyung-Tae;Chang, Sung-Goo;Jung, Jee-Chang
    • YAKHAK HOEJI
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    • v.42 no.5
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    • pp.494-499
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    • 1998
  • As part of a drug discovery program to discover more effective platinum-based anticancer drugs, a series of platinum complexes of 1,2-bis(diphenylphosphino)ethane(1,2-diaminopro pane)platinum(II)dinitrate (KHPC-070) has been evaluated in vitro against various tumor cell lines and normal kidney cells. The structure of this new compound was determined by elemental analysis, infrared spectroscopy (IR) and $^{13}carbon$ nuclear magnetic resonance (NMR). With the use of nine tumor cell lines, KHPC-070 exhibited a comparable cytotoxic to cisplatin. The cytotoxicity of KHPC-070 in normal cells was quite less than that of cisplatin using 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and [$^3H$]-thymidine uptake tests in rabbit renal proximal tubular cells and human renal cortical cells. Based on these results, KHPC-070 is considered to have more selective cytotoxicity toward cancer cells than normal human/rabbit kidney cells.

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Anti-inflammatory Effect of Imyosan Extract is more potent than that of its Component Herb Extracts in Murine Macrophages (마우스 대식세포인 RAW 264.7에 대한 이묘산(二妙散)의 메탄올 추출물의 항염증 효과)

  • Yun, Hyun-Jeong;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.23 no.3
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    • pp.163-173
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    • 2008
  • Objectives : Imyosan (IMS), a drug preparation comprised of Phellodendri Cortex (PC) and Atractylodis Rhizoma (AR), is commonly used as a traditional herbal medicine in Korea and China for the treatment of various inflammatory diseases. However, little is known about the effect of IMS and its component herbs on inflammatory mediators in RAW 264.7 cells. Therefore, in this study, methanol extracts of IMS and its component herbs were examined to determine if they inhibited inflammatory effects in RAW 264.7 cells. Methods : Cytotoxic activity of IJHT and its components on RAW 264.7 cells was using 5-(3-carboxymethoxyphenyl)-2H-tetrazolium inner salt (MTS) assay. The nitric oxide (NO) production was measured by Griess reagent system. And proinflammatory cytokines were measured by ELISA kit. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were detected by western blot. Results : Methanol extract of IMS and its component herbs were significantly reduced iNOS and COX-2 expression as well as NO, PGE2, $IL-1{\beta}$ and IL-6 production in RAW 264.7 cells. Conclusions : The results of this study indicated that the anti-inflammatory effect of Imyosan extract is more potent than that of extracts of its component herbs in macrophages.

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