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The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients

  • Lee, Choong-kun;Chon, Hong Jae;Kwon, Woo Sun;Ban, Hyo-Jeong;Kim, Sang Cheol;Kim, Hyunwook;Jeung, Hei-Cheul;Chung, Jimyung;Rha, Sun Young
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.29.1-29.12
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    • 2022
  • Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3 and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of toxicity such as severe diarrhea or neutropenia.

Genome characterization and mutation analysis of human influenza A virus in Thailand

  • Rattanaburi, Somruthai;Sawaswong, Vorthon;Nimsamer, Pattaraporn;Mayuramart, Oraphan;Sivapornnukul, Pavaret;Khamwut, Ariya;Chanchaem, Prangwalai;Kongnomnan, Kritsada;Suntronwong, Nungruthai;Poovorawan, Yong;Payungporn, Sunchai
    • Genomics & Informatics
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    • v.20 no.2
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    • pp.21.1-21.14
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    • 2022
  • The influenza A viruses have high mutation rates and cause a serious health problem worldwide. Therefore, this study focused on genome characterization of the viruses isolated from Thai patients based on the next-generation sequencing technology. The nasal swabs were collected from patients with influenza-like illness in Thailand during 2017-2018. Then, the influenza A viruses were detected by reverse transcription-quantitative polymerase chain reaction and isolated by MDCK cells. The viral genomes were amplified and sequenced by Illumina MiSeq platform. Whole genome sequences were used for characterization, phylogenetic construction, mutation analysis and nucleotide diversity of the viruses. The result revealed that 90 samples were positive for the viruses including 44 of A/H1N1 and 46 of A/H3N2. Among these, 43 samples were successfully isolated and then the viral genomes of 25 samples were completely amplified. Finally, 17 whole genomes of the viruses (A/H1N1, n=12 and A/H3N2, n=5) were successfully sequenced with an average of 232,578 mapped reads and 1,720 genome coverage per sample. Phylogenetic analysis demonstrated that the A/H1N1 viruses were distinguishable from the recommended vaccine strains. However, the A/H3N2 viruses from this study were closely related to the recommended vaccine strains. The nonsynonymous mutations were found in all genes of both viruses, especially in hemagglutinin (HA) and neuraminidase (NA) genes. The nucleotide diversity analysis revealed negative selection in the PB1, PA, HA, and NA genes of the A/H1N1 viruses. High-throughput data in this study allow for genetic characterization of circulating influenza viruses which would be crucial for preparation against pandemic and epidemic outbreaks in the future.

A Study on the Error Rate of Non-destructive Rebar Detection Under Different Environmental Factors (환경적 요인에 따른 비파괴 철근 탐사의 오차율에 관한 연구)

  • Kang, Beom-Ju;Kim, Young-Hwan;Kim, Young-Min;Park, Kyung-Han;Oh, Hong-Seob
    • Journal of the Korean Recycled Construction Resources Institute
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    • v.9 no.4
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    • pp.506-513
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    • 2021
  • The durability and safety of reinforced concrete structures significantly depend on the reinforcement conditions, concrete cover thickness, cracks, and concrete strength. There are two ways to accurately determine the information on reinforcing bars embedded in concrete - the local destructive method and the non-destructive rebar detection test. In general, the non-destructive rebar detection tests, such as the electromagnetic wave radar method, electromagnetic induction method, and radiation method, are adopted to avoid damage to the structural elements. The moisture content and temperature of concrete affect the dielectric constant, which is the electrical property of concrete, and cause interference in the non-destructive rebar detection test results. Therefore, in this study, the effects of the electromagnetic wave radar method and electromagnetic induction method have been analyzed according to the temperature and surface moisture content of concrete. Due to the technological advancement and development of equipment, the average error rate was less than 5% in the specimens at 24℃, irrespective of their operating principles. Among the tested methods, the electromagnetic induction method showed very high accuracy. The electromagnetic wave radar method indicated a relatively small error rate in the dry state than in the wet state, and exhibited a relatively high error rate at high temperatures. It was confirmed that the error could be reduced by applying the electromagnetic wave radar method when the temperature of the probe was low and in a dry state, and by using the electromagnetic induction method when the probe was in a wet state or at a high temperature.

Comparison of Conventional Culture Method, Enzyme Immune Method, and PCR for the Rapid Detection of Salmonella spp. in Pet Food (반려동물 사료의 Salmonella spp. 신속검출을 위한 증균배양법, 면역학적 검출법 및 종 특이 프라이머를 이용한 PCR 방법 비교)

  • Yun, Hyejeong;Cha, Sun Ho;Lee, Seung-Hwa;Jeong, Min-Hee;Na, Tae-Woong;Kim, Haejin;Cho, Hyunjeong;Hong, Seong-Hee
    • Journal of Food Hygiene and Safety
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    • v.37 no.1
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    • pp.15-20
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    • 2022
  • The purpose of this study was to compare the conventional culture method, enzyme immune method and the PCR method using species-specific primer in the analysis on the Salmonella spp. found in domestically distributed pet foods. For the study, Salmonella spp. were detected from 175 samples. From the conventional culture method and the PCR method, two samples (jerky and corn gluten) were determined as positive. Also, from the enzyme immune method, one sample (corn gluten) was test-positive. The study revealed that application of the PCR method with species-specific primer allows better distinguishment between the species of the strain collected from the samples than the conventional culture method and/or the enzyme immune method.

Phylogenetic and pathogenic traits of YHV3 and IHHNV detected from imported frozen shrimp (수입 냉동새우에서 검출된 YHV3와 IHHNV의 계통학 및 병원성 분석)

  • Baek, Eun Jin;Joeng, Ye Jin;Jeong, Min A;Park, Ji Yeon;Kim, Kwang Il
    • Journal of fish pathology
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    • v.35 no.1
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    • pp.27-40
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    • 2022
  • Yellow head virus (YHV), Infectious hypodermal and hematopoietic necrosis (IHHNV), Taura syndrome virus (TSV), and Infectious myositis virus (IMNV) cause serious mortality to Penaeidae shrimp in the aquaculture. In this study, YHV, IHHNV, TSV, and IMNV were surveyed from imported frozen shrimps between 2019 and 2020 via molecular diagnostic assay. Among 10 shrimp groups, YHV (n=1) and IHHNV (n=4) were detected by RT-PCR and PCR, respectively. From the phylogenetic analysis based on the partial ORF 1b region of YHV, YHV was classified into YHV genotype 3 (YHV3). And IHHNVs (n=2) detected from Litopenaeus vannamei belong to infectious IHHNV type 2. Although IHHNVs (n=2) identified from Penaeus monodon showed PCR positive results (MG 831F/R primer set), the sequences of ORF 2 and 3 were not amplified, suggesting that those samples might possess type A IHHNV related sequence of P. monodon. Furthermore, in the challenge test, even though PCR-detected isolates (YHV3/type A IHHNV related sequence or infectious IHHNV type 2) were not induced mortality to L. vannamei, viral genes were amplified suggesting that the viruses in the frozen shrimp could be non-pathogenic particles which are not enough to induce mortality.

Design Optimization to achieve an enhanced flatness of a Lab-on-a-Disc for liquid biopsy (액체생검용 Lab-on-a-Disc의 평탄도 향상을 위한 최적화)

  • Seokkwan Hong;Jeong-Won Lee;Taek Yong Hwang;Sung-Hun Lee;Kyung-Tae Kim;Tae Gon Kang;Chul Jin Hwang
    • Design & Manufacturing
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    • v.17 no.1
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    • pp.20-26
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    • 2023
  • Lab-on-a-disc is a circular disc shape of cartridge that can be used for blood-based liquid biopsy to diagnose an early stage of cancer. Currently, liquid biopsies are regarded as a time-consuming process, and require sophisticated skills to precisely separate cell-free DNA (cfDNA) and circulating tumor cells (CTCs) floating in the bloodstream for accurate diagnosis. However, by applying the lab-on-a-disc to liquid biopsy, the entire process can be operated automatically. To do so, the lab-on-a-disc should be designed to prevent blood leakage during the centrifugation, transport, and dilution of blood inside the lab-on-a-disc in the process of liquid biopsy. In this study, the main components of lab-on-a-disc for liquid biopsy are fabricated by injection molding for mass production, and ultrasonic welding is employed to ensure the bonding strength between the components. To guarantee accurate ultrasonic welding, the flatness of the components is optimized numerically by using the response surface methodology with four main injection molding processing parameters, including the mold & resin temperatures, the injection speed, and the packing pressure. The 27 times finite element analyses using Moldflow® reveal that the injection time and the packing pressure are the critical factors affecting the flatness of the components with an optimal set of values for all four processing parameters. To further improve the flatness of the lab-on-a-disc components for stable mass production, a quarter-disc shape of lab-on-a-disc with a radius of 75 mm is used instead of a full circular shape of the disc, and this significantly decreases the standard deviation of flatness to 30% due to the reduced overall length of the injection molded components by one-half. Moreover, it is also beneficial to use a quarter disc shape to manage the deviation of flatness under 3 sigma limits.

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Comparison of Genome-wide Association Study (GWAS) Algorithms for Detecting Genetic Variants Associated with Growth Traits in Olive Flounder Paralichthys olivaceus (넙치(Paralichthys olivaceus)의 성장형질 연관 유전자 변이 탐색을 위한 전장유전체연관분석(GWAS) 알고리즘 비교 분석 연구)

  • Sangwon Yoon;Heegun Lee;Jong-Won Park;Minhwan Jeong;Dain Lee;Hyo Sun Jung;Julan Kim;Hye-Rim Yang;Seung Hwan Lee;Jeong-Ho Lee
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.56 no.4
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    • pp.411-418
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    • 2023
  • Genome wide association studies (GWAS) identify genetic loci associated with quantitative traits in genomic selection. Although several studies have compared performance of various algorithms, no study compares them in olive flounder Paralichthys olivaceus. This study compared the GWAS results of four mixed linear model (MLM) algorithms and one Fixed and random model Circulating Probability Unification (FarmCPU) algorithm in olive flounder. Considering gender and genetic association matrices as fixed and random effects, the MLM had stable performance without inflation for λGC (genomic inflation factor) of -log10P. The FarmCPU algorithm had some appropriate λGC of -log10P, and an upward tail was identified in quantile-quantile plots. Therefore, the models were suitable for detecting genetic variants associated with olive flounder growth traits. Moreover, significant genotypes appeared several times at chromosome 22, around which quantitative trait loci are expected to exist. Finally, in both models, some of the most genetic variants were found in genes related to growth traits, confirming their reliability. These results will be helpful when applied to the genomic selection of olive flounder growth traits in the future.

Molecular Characterization of an Avian-origin Reassortant H7N1 Influenza Virus (조류 유래 재조합 H7N1 인플루엔자 바이러스의 분자적 특성 규명)

  • Sun-Woo Yoon
    • Journal of Life Science
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    • v.33 no.8
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    • pp.605-611
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    • 2023
  • Recently, sporadic cases of human infection by genetic reassortants of H7Nx influenza A viruses have been reported; such viruses have also been continuously isolated from avian species. In this study, A/wild bird/South Korea/sw-anu/2023, a novel reassortant of the H7N1 avian influenza virus, was analyzed using full-genome sequencing and molecular characterization. Phylogenetic analysis showed that A/wild bird/South Korea/sw-anu/2023 belonged to the Eurasian lineage of H7Nx viruses. The polymerase basic (PB)2, PB1, polymerase acidic (PA), and nucleoprotein (NP) genes of these viruses were found to be closely related to those of avian influenza viruses isolated from wild birds, while the hemagglutinin (HA), neuraminidase (NA), matrix (M), and nonstructural (NS) genes were similar to those of avian influenza viruses isolated from domestic ducks. In addition, A/wild bird/South Korea/sw-anu/2023 also had a high binding preference for avian-specific glycans in the solid-phase direct binding assay. These results suggest the presence of a new generation of H7N1 avian influenza viruses in wild birds and highlight the reassortment of avian influenza viruses found along the East Asian-Australasian flyway. Overall, H7Nx viruses circulate worldwide, and mutated H7N1 avian viruses may infect humans, which emphasizes the requirement for continued surveillance of the H7N1 avian influenza virus in wild birds and poultry.

Development of simultaneous detection method for living modified cotton varieties MON757, MON88702, COT67B, and GHB811 (유전자변형 면화 MON757, MON88702, COT67B, GHB811의 동시검출법 개발)

  • Il Ryong Kim;Min-A Seol;A-Mi Yoon;Jung Ro Lee;Wonkyun Choi
    • Korean Journal of Environmental Biology
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    • v.39 no.4
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    • pp.415-422
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    • 2021
  • Cotton is an important fiber crop, and its seeds are used as feed for dairy cattle. Crop biotechnology has been used to improve agronomic traits and quality in the agricultural industry. The frequent unintentional release of LM cotton into the environment in South Korea is attributed to the increased application of living modified (LM) cotton in food, feed, and processing industries. To identify and monitor the LM cotton, a method for detecting the approved LM cotton in South Korea is required. In this study, we developed a method for the simultaneous detection of four LM cotton varieties, MON757, MON88702, COT67B, and GHB811. The genetic information of each LM event was obtained from the European Commission-Joint Research Centre and Animal and Plant Quarantine Agency. We designed event-specific primers to develop a multiplex PCR method for LM cotton and confirmed the specific amplification. Using specificity assay, random reference material(RM) mixture analysis and limit of detection(LOD), we verified the accuracy and specificity of the multiplex PCR method. Our results demonstrate that the method enabled the detection of each event and validation of the specificity using other LM RMs. The efficiency of multiplex PCR was further verified using a random RM mixture. Based on the LOD, the method identified 25 ng of template DNA in a single reaction. In summary, we developed a multiplex PCR method for simultaneous detection of four LM cotton varieties, for possible application in LM volunteer analysis.

Toxicity assessment of food additive(E171) in aquatic environments (식품첨가물 E171이 수생물에 미치는 독성 평가)

  • In-Gyu Song;Kanghee Kim;Hakwon Yoon;June-Woo Park
    • Korean Journal of Environmental Biology
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    • v.41 no.1
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    • pp.41-53
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    • 2023
  • E171, a mixture of titanium dioxide, has been widely used as a food additive due to its whitening effect and low toxicity. However, it has been proven that E171 is no longer safe for public health. So far, there are insufficient studies on the toxic effects of E171 on organisms especially using standardized test methods. In this study, toxicity assessments of E171 to two aquatic species, water flea (Daphnia magna) and zebrafish (Danio rerio), were performed using modified standardized test methods based on the physicochemical properties of E171. The hydrodynamic diameter, polydispersity index, and turbiscan stability index (TSI) were measured to ensure the dispersion stability of E171 in exposure media during the test period. The EC50 for immobilization of water flea was 141.7 mg L-1 while zebrafish was not affected until 100 mg L-1 of E171. Measurements of reactive oxygen species (ROS) and antioxidant enzyme activities confirmed that E171 induced oxidative stress, leading to the activation of superoxide dismutase and catalase in both water flea and zebrafish, although the expression of antioxidant enzyme genes differed between species. These results suggested the potential risk of E171 to aquatic organisms and provided toxicological insights into the impacts of E171 on the environment.