• Title/Summary/Keyword: Targeted agent

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Gene Expression Analysis of Anticancer Drug Induced Hepatotoxicity Using cDNA Microarray

  • Lee, Gyoung-Jae;Kim, Yang-Suk;Jung, Jin-Wook;Hwang, Seung-Yong;Park, Joon-Suk;Kang, Kyung-Sun;Lee, Yong-Soon;Chon, Man-Suk;Chon, Kum-Jin;Kang, Jong-Soo;Kim, Dong-Hyean;Park, Young-Keun
    • Molecular & Cellular Toxicology
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    • v.2 no.2
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    • pp.141-149
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    • 2006
  • Tamoxifen (TAM), a non-steroidal anti estrogen anticancer drug and chemopreventive agent for breast cancer, have caused cholestasis in liver. The potent hepatocarcinogenicity of this drug has been reported. Methotrexate (MTX) is dihydrofolate reductase inhibitor which interfaces with the synthesis for urine nucleotide and dTMP. And it may cause atrophy, necrosis and steatosis in liver. These two anticancer drug have well-known hepatotoxicity. So, in this study we compare the gene expression pattern of antitumor agent TAM and MTX, using the cDNA microarray. We have used 4.8 K cDNA microarray to identify hepatotoxicity-related genes in 5-week-old male Sprague-Dawley (SD) rats. Confirm the pattern of gene expression, we have used Real time PCR for targeted gene. In the case of MTX, Protease related gene (Ctse, Ctsk) and Protein kinase (Pctk 1) have shown specific expression pattern. And in the case of TAM, apoptosis related gene (Pdcd 8) and signal transduction related gene (kdr) have significantly up regulated during treatment time. Gene related with growth factor, lipid synthesis, chemokins were significantly changed. From the result of this study, the information about influence of TAM and MTX to hepatoxicity will provide.

Design and Implementation of VR-ADHD Digital Therapy Using VR Games

  • Dae-Won Park;Han-Byul Kang;Sang-Hyun Lee
    • International Journal of Advanced Culture Technology
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    • v.11 no.1
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    • pp.332-336
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    • 2023
  • In this paper, we design and implement an ADHD diagnostic rating scale algorithm and virtual reality- based digital treatment by combining virtual reality technology that enables multiple access based on specialized medical data. The VR ADHD digital treatment to be implemented is intended to be applied directly to diagnosis and treatment of child/adolescent ADHD by applying various psychiatric treatment technologies. In order to evaluate the usability of the digital therapeutic agent developed in this paper, an expert group consisting of 2 males and 12 females "targeted counseling psychology majors at the Asian Dementia Center once a day for 3 weeks, ADHD VR-based digital therapeutics for children Experienced and usability evaluation conducted. As a final result of this thesis, it was possible to develop attentional concentration ability, working memory improvement ability, and impulsive control ability in four games of digital therapy, and it was possible to confirm significant results that can be expected to have ADHD therapeutic effects.

Compressive and Adhesive Strengths of Mortars using Re-emulsification Type Polymer and Ultra-Rapid-Hardening Cement (재유화형 분말수지와 초속경 시멘트를 혼입한 모르타르의 압축강도 및 접착강도 특성)

  • Lee, Kwang-Il;Yoon, Hyun-Sub;Yang, Keun-Hyeok
    • Journal of the Korea Institute of Building Construction
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    • v.18 no.4
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    • pp.329-335
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    • 2018
  • The objective of this study is to develop a mortar mixture with high workability and adhesive strength for section jacketing in seismic strengthening technology of existing concrete structures. To achieve targeted requirements of the mortars (initial flow exceeding 200 mm, compressive strength of 30MPa, and adhesive strength exceeding 1MPa), step-by-step tests were conducted under the variation of the following mixture parameters: water-to-binder ratio, sand-to-binder ratio, polymer-to-binder ratio, dosage of viscosity agent, and content of ultra-rapid-hardening cement. The adhesive strength of the mortars was also estimated with respect to the various surface treatment states of existing concrete. Based on the test results, the mortar mixture with the polymer-to-binder ratio of 10% and the content of ultra-rapid-hardening cement of 5% can be recommended for the section jacketing materials. The recommended mortar mixture satisfied the targeted requirements as follows: initial flow of 220 mm, high-early strength gain, 28-day compressive strength of 35MPa, and adhesive strength exceeding 1.2MPa.

Application of the rpoS Gene for Species-Specific Detection of Vibrio vulnificus by Real-Time PCR

  • Kim, Dong-Gyun;Ahn, Sun-Hee;Kim, Lyoung-Hwa;Park, Kee-Jai;Hong, Yong-Ki;Kong, In-Soo
    • Journal of Microbiology and Biotechnology
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    • v.18 no.11
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    • pp.1841-1847
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    • 2008
  • Vibrio vulnificus is a causative agent of serious diseases in humans, resulting from the contact of wound with seawater or consumption of raw seafood. Several studies aimed at detecting V. vulnificus have targeted vvh as a representative virulence toxin gene belonging to the bacterium. In this study, we targeted the rpoS gene, a general stress regulator, to detect V. vulnificus. PCR specificity was identified by amplification of 8 V. vulnificus templates and by the loss of a PCR product with 36 non-V. vulnificus strains. The PCR assay had the 273-bp fragment and the sensitivity of 10 pg DNA from V. vulnificus. SYBR Green I-based real-time PCR assay targeting the rpoS gene showed a melting temperature of approximately $84^{\circ}C$ for the V. vulnificus strains. The minimum level of detection by real-time PCR was 2 pg of purified genomic DNA, or $10^3$ V. vulnificus cells from pure cultured broth and $10^3$ cells in 1 g of oyster tissue homogenates. These data indicate that real-time PCR is a sensitive, species-specific, and rapid method for detecting this bacterium, using the rpoS gene in pure cultures and in infected oyster tissues.

Functional Modification of a Specific RNA with Targeted Trans-Splicing

  • Park, Young-Hee;Kim, Sung-Chun;Kwon, Byung-Su;Jung, Heung-Su;Kim, Kuchan;Lee, Seong-Wook
    • Genomics & Informatics
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    • v.2 no.1
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    • pp.45-52
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    • 2004
  • The self-splicing group I intron from Tetrahymena thermophila has been demonstrated to perform splicing reaction with its substrate RNA in the trans configuration. In this study, we explored the potential use of the trans-splicing group I ribozymes to replace a specific RNA with a new RNA that exerts any new function we want to introduce. We have chosen thymidine phosphorylase (TP) RNA as a target RNA that is known as a valid cancer prognostic factor. Cancer-specific expression of TP RNA was first evaluated with RT-PCR analysis of RNA from patients with gastric cancer. We determined next which regions of the TP RNA are accessible to ribozymes by employing an RNA mapping strategy, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. A specific ribozyme recognizing the most accessible sequence in the TP RNA with firefly luciferase transcript as a 3' exon was then developed. The specific trans-splicing ribozyme transferred an intended 3' exon tag sequence onto the targeted TP transcripts, resulting in a more than two fold induction of the reporter activity in the presence of TP RNA in mammalian cells, compared to the absence of the target RNA. These results suggest that the Tetrahymena ribozyme can be a potent anti-cancer agent to modify TP RNAs in tumors with a new RNA harboring anti-cancer activity.

A Study on thinner's Physicochemical property and its effect on genital organ of rat (시너(thinner)의 물리화학적 특성과 랫트의 생식기에 미치는 영향 연구)

  • Kim, Hyeon-Yeong;Lee, Sung-Bae;Han, Jeong-Hee;Kim, Tae-Gyun;Lee, Jung-Suk;Kang, Min-Gu;Lee, Chae-Kwan
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.18 no.3
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    • pp.224-238
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    • 2008
  • The aim of this study is to confirm the physicochemical property and hazard of thinner (012), which is a diluent of enamel paint used for floor coating for waterproofing and oil painting for the outer wall. The literatures of physicochemical property and hazard of thinner were surveyed and its physicochemical property were evaluated. And then, the inhalation toxicity of thinner affecting the central nervous system and reproductive organs in rats were examined by subchronic (6 h./day. 5 days/ week for 13 weeks) inhalation test. 1) According to the 13-week subchronic inhalation test, there were no significant changes in clinical test and body weight. However, a significant evidence of toxicity was observed in the hematological test and organ weight such as heart, kidney, liver and brain (p<0.01) in the 200 ppm and 1,000 ppm exposure groups in a dose response manner. In the histopathology analysis, there were no significant evidence of toxicity. Therefore, thinner was not classified as an organ targeted toxic agent. In case of Harmfulness, it could be classified as a chronic toxic agent 3($500 ppm/4hr, rat). 2) The reproductive toxicity such as extension of the period of estrous cycle, reduction of serum estradiol concentration and increase of frequency of the abnormal sperm was observed in the 1,000 ppm exposed animals. 3) The result of the physicochemical property of the test material showed that the specific gravity was 0.793, boiling point $155.8^{\circ}C$, steam pressure 2.1 kPa, ignition point $34.5^{\circ}C$, and spontaneous ignition point $280^{\circ}C$. The endothermic and exothermic values were 371.4 J/g and 159.1 J/g. respectively. The explosion limit was 214 mg/l. These data showed that thinner could be classified as an explosion agent level 1.2 and ignitive liquid agent 3 ($23-60^{\circ}C$) according to the notification No. 2008-1 of the Labor Ministry, "Classifying Standard of Chemical Materials."

Recovery of Genes Epigenetically Altered by the Histone Deacetylase Inhibitor Scriptaid and Demethylating Agent 5-Azacytidine in Human Leukemia Cells

  • Park, Eun-Kyung;Jeon, Eun-Hyung;Kim, In-Ho;Park, Seon-Yang
    • Genomics & Informatics
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    • v.8 no.4
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    • pp.185-193
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    • 2010
  • Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD, CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.

Transferrin-Conjugated Liposome/IL-12 pDNA Complexes for Cancer Gene Therapy in Mice

  • Joo, Soo-Yeon;Kim, Jin-Seok;Park, Heon-Joo;Choi, Eun-Kyung
    • Macromolecular Research
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    • v.13 no.4
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    • pp.293-296
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    • 2005
  • Transferrin ($T_{f}$) has been used as a targeting ligand for delivering liposome/interleukin-12 (IL-12) pDNA complexes to cancer cells mostly due to the greater number of transferrin receptors ($T_{f}R$) found on tumor cells than on normal cells. $T_{f}$ was conjugated to liposomes via the reaction of MPB-PE with thiol groups of $T_{f}$ introduced by a heterobifunctional cross-linking agent, N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). Four days after C26 inoculation when the tumor volume reached ${\sim}100mm^{3}$, tumor-bearing Balb/c mice were injected intravenously with $T_{f}-liposome/IL-12 pDNA$complexes twice a week for 3 weeks. Significant suppression of tumor growth was achieved in the group treated with the $T_{f}-liposome/IL-12 pDNA$ complexes, with a dose of $10{\mu}g$ of IL-12 pDNA showing the highest suppression effect among the tested doses. Similar results were obtained when the therapy was initiated one day after tumor inoculation, although in this case $30{\mu}g$ IL-12 pDNA/$T_{f}-liposome$ complexes showed a significant suppression of tumor growth between 19 and 23 days after tumor inoculation. This result indicates that the transferrin receptor-targeted liposomal system is an efficient delivery agent of therapeutic genes, such as IL-12, in mice and that its potential clinical use warrants further research investigation.

Immunotherapy for Advanced/Metastatic Esophageal Squamous Cell Carcinoma (진행성/전이성 식도 편평상피세포암의 면역치료)

  • Sung Eun Kim;Kyoungwon Jung;Moo In Park
    • Journal of Digestive Cancer Research
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    • v.12 no.2
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    • pp.72-81
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    • 2024
  • Esophageal squamous cell carcinomas constitute a major proportion of esophageal cancers in Korea. Conventional chemotherapy and radiation therapy are the options for treating advanced/metastatic esophageal cancer, but the prognosis remains poor. Immunotherapy has significantly improved the prognosis of several advanced/metastatic cancers including esophageal squamous cell carcinoma. In Korea, immunotherapy is used to treat advanced/metastatic esophageal squamous cell carcinoma, and treatment results are expected to further improve. Immunotherapy is a term used to describe a treatment modality involving a biological/targeted agent that aims to enhance and restore the ability of the immune system to detect and destroy cancer cells by modifying or blocking co-stimulating signals. Immune checkpoint inhibitors have revolutionized cancer treatment with the administration of a single agent (monotherapy) or combinations of multiple agents, with the three approved agents being anti-PD-1 (programmed death 1), anti-PD-L1 (programmed cell death ligand 1), and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) monoclonal antibodies. Anti-PD-1 drugs including nivolumab and pembrolizumab have been mainly investigated for treating advanced/metastatic esophageal squamous cell cancer. Studies on their effectiveness in a neoadjuvant setting, a curative adjuvant setting, or as the first-line treatment for advanced or metastatic setting are ongoing. This review describes the principle of action, summary of existing clinical studies, and prospects for immune checkpoint inhibitors used in the treatment of advanced/metastatic esophageal squamous cell cancer.

Utilizing OpenFlow and sFlow to Detect and Mitigate SYN Flooding Attack

  • Nugraha, Muhammad;Paramita, Isyana;Musa, Ardiansyah;Choi, Deokjai;Cho, Buseung
    • Journal of Korea Multimedia Society
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    • v.17 no.8
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    • pp.988-994
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    • 2014
  • Software Defined Network (SDN) is a new technology in computer network area which enables user to centralize control plane. The security issue is important in computer network to protect system from attackers. SYN flooding attack is one of Distributed Denial of Service attack methods which are popular to degrade availability of targeted service on Internet. There are many methods to protect system from attackers, i.e. firewall and IDS. Even though firewall is designed to protect network system, but it cannot mitigate DDoS attack well because it is not designed to do so. To improve performance of DDOS mitigation we utilize another mechanism by using SDN technology such as OpenFlow and sFlow. The methodology of sFlow to detect attacker is by capturing and sum cumulative traffic from each agent to send to sFlow collector to analyze. When sFlow collector detect some traffics as attacker, OpenFlow controller will modify the rule in OpenFlow table to mitigate attacks by blocking attack traffic. Hence, by combining sum cumulative traffic use sFlow and blocking traffic use OpenFlow we can detect and mitigate SYN flooding attack quickly and cheaply.