31 results on '"Udagawa C"'
Search Results
2. Lipid nanoparticles for delivering antitumor drugs
- Author
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Hodoshima, N., primary, Udagawa, C., additional, Ando, T., additional, Fukuyasu, H., additional, Watanabe, H., additional, and Nakabayashi, S., additional
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- 1997
- Full Text
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3. Polymorphisms of canine BRCA2 BRC repeats affecting interaction with RAD51
- Author
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Ochiai, K., Ishiguro-Oonuma, T., Yoshikawa, Y., Udagawa, C., Kato, Y., Watanabe, M., Bonkobara, M., Morimatsu, M., and Toshinori Omi
4. Lipid nanoparticles for delivering antitumor drugs
- Author
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Hodoshima, N., Udagawa, C., Ando, T., Fukuyasu, H., Watanabe, H., and Nakabayashi, S.
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Drugs -- Vehicles ,Antineoplastic agents -- Dosage and administration -- Research ,Drug delivery systems -- Research ,Antimitotic agents -- Dosage and administration -- Research ,Health ,Research ,Dosage and administration - Abstract
Hodoshima, N.; Udagawa, C.; Ando, T.; Fukuyasu, H.; Watanabe, H.; Nakabayashi, S. 'Lipid Nanoparticles for Delivering Antitumor Drugs.' International Journal of Pharmaceutics, January 1, 1997;146(1):81-92. According to the authors' abstract [...]
- Published
- 1997
5. Population genetics for 18 short tandem repeat loci (Canine Genotypes TM Panel 2.1 Kit) of 150 unrelated dogs from three pure-bred groups in Japan.
- Author
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Kunita F, Udagawa C, Inagaki T, Suzuki H, Bonkobara M, and Omi T
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- Animals, Dogs genetics, Japan, Genetics, Population, Gene Frequency, Breeding, DNA Fingerprinting methods, Microsatellite Repeats genetics, Genotype
- Abstract
Similar to that in Europe and the United States, the need for forensic DNA identification in dogs is increasing in Japan. As few studies have used commercial genotyping kits, the effectiveness of the Canine Genotypes
TM Panel 2.1 Kit for individual DNA identification in dogs bred in Japan was examined. We genotyped 150 unrelated dogs (50 Golden Retrievers, 50 Miniature Dachshunds, and 50 Shiba Inu) at 18 canine short tandem repeat loci by the Kit. The allele frequency, expected heterozygosity, observed heterozygosity, p-value, power of the discriminant, and of exclusion, polymorphic information content, and random matching probability were calculated for each marker. The random matching probability was subsequently estimated to be 4.394×10-22 in the 150 dogs of the three pure-bred groups based on 18 STR loci; 3.257 × 10-16 in the Golden Retriever, 3.933 × 10-18 in the Miniature Dachshund, and 2.107 × 10-18 in the Shiba Inu breeds. In addition, principal component analysis based on genotype data revealed the Golden Retrievers, Miniature Dachshunds, and Shiba Inus separated into three clusters. The results of the genotype analysis showed that the Canine GenotypesTM Panel 2.1 Kit could be useful for identity testing and tool of population study of canines in Japan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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6. Association between genetic variants and the risk of nivolumab-induced immune-related adverse events.
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Udagawa C, Nakano MH, Yoshida T, Ohe Y, Kato K, Mushiroda T, and Zembutsu H
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- Humans, Cohort Studies, Retrospective Studies, Nivolumab adverse effects, Genome-Wide Association Study
- Abstract
Aim: We sought to identify the variants that could predict the risk of nivolumab-induced immune-related adverse events (irAEs) in patients with cancer. Patients & methods: We enrolled 622 Japanese patients and carried out a genome-wide association study. The associations for 507 single nucleotide polymorphisms (SNPs) showing p < 0.001 were further investigated using an independent cohort. Results: In the combined analysis, possible associations were found for a total of 90 SNPs. Although no SNPs were identified to be significantly associated with nivolumab-induced irAEs, the SNP most strongly associated with nivolumab-induced irAEs was rs469490. Conclusion: This study is an important hypothesis-generating study to guide future studies in larger and/or other ethnic cohorts.
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- 2022
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7. The association of four genetic variants with myelosuppression in gemcitabine-treated Japanese is not evident in gemcitabine/carboplatin-treated Swedes.
- Author
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Björn N, Jakobsen I, Udagawa C, Brandén E, Koyi H, Lewensohn R, De Petris L, Zembutsu H, and Gréen H
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- Antineoplastic Combined Chemotherapy Protocols, Carboplatin adverse effects, Deoxycytidine analogs & derivatives, Humans, Japan, Sweden, Gemcitabine, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Neutropenia chemically induced, Neutropenia drug therapy, Neutropenia genetics
- Abstract
Gemcitabine/carboplatin-induced myelosuppressive adverse drug reactions (ADRs) are clinical problems leading to patient suffering and dose alterations. There is a need for personalised medicine to improve treatment effects and patients' well-being. We tested four genetic variants, rs11141915, rs1901440, rs12046844 and rs11719165, previously suggested as potential biomarkers for gemcitabine-induced leukopenia/neutropenia in Japanese patients, in 213 Swedish gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients. DNA was genotyped using TaqMan probes and real-time PCR. The relationships between the risk alleles and low toxicity (non-ADR: Common Terminology Criteria for Adverse Events [CTCAE] grades 0) or high toxicity (ADR: CTCAE grades 3-4) of platelets, leukocytes and neutrophils were evaluated using Fisher's exact test. The risk alleles did not correlate with myelosuppression, and the strongest borderline significance (not withstanding adjustment for multiple testing) was for rs1901440 (neutropenia, p = 0.043) and rs11719165 (leukopenia, p = 0.049) where the risk alleles trended towards lower toxicity, contrasting with previous study findings. Risk alleles and higher risk scores were more common among our patients. We conclude that the genetic variants do not apply to Swedish patients treated with gemcitabine/carboplatin. However, they can still be important in other populations and cohorts, especially in a gemcitabine monotherapy setting, where the causal genetic variation might influence myelosuppressive ADRs., (© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
- Published
- 2022
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8. Replication Study for the Association of Five SNPs Identified by GWAS and Trastuzumab-Induced Cardiotoxicity in Japanese and Singaporean Cohorts.
- Author
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Udagawa C, Kuah S, Shimoi T, Kato K, Yoshida T, Nakano MH, Shimo A, Kojima Y, Yoshie R, Tsugawa K, Mushiroda T, Tan EY, and Zembutsu H
- Subjects
- Genome-Wide Association Study, Humans, Japan, Neoplasms drug therapy, Neoplasms genetics, Receptor, ErbB-2 genetics, Singapore, Cardiotoxicity, Polymorphism, Single Nucleotide, Trastuzumab adverse effects
- Abstract
Trastuzumab (herceptin) is an effective drug for human epidermal growth factor receptor type 2 (HER2)-positive cancer. However, cardiotoxicity remains a serious complication. In our previous genome-wide association study (GWAS), we identified potential associations for five single nucleotide polymorphisms (SNPs) with trastuzumab-induced cardiotoxicity in a Japanese population. To validate this association, here we performed replication studies using Japanese and Singaporean case-control cohorts (Japan: 6 cases and 206 controls; Singapore: 22 cases and 178 controls). Although none of the SNPs showed a statistically significant association with trastuzumab-induced cardiotoxicity, we show that three (rs8032978, rs7406710 and rs9316695) and four (rs8032978, rs7406710, rs28415722 and rs11932853) SNPs had an effect in the same direction in the Japanese and the Singaporean cohort, respectively, as that in our previous study. Combining the previous study with the current replication studies, we find a strong association for two SNPs, rs8032978 and rs7406710, with trastuzumab-induced cardiotoxicity (P
combined = 4.92 × 10-5 and 5.50 × 10-5 , respectively). These data suggest that rs8032978 and rs7406710 could be predictive markers of trastuzumab-induced cardiotoxicity in Japanese and Singaporean populations, and support their potential use in clinical risk assessment. These findings offer a first step toward the development of clinically available markers for the potential risk of trastuzumab-induced cardiotoxicity as well as an improved understanding of the pathogenesis of this complication.- Published
- 2022
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9. Unfolding is the driving force for mitochondrial import and degradation of the Parkinson's disease-related protein DJ-1.
- Author
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Queliconi BB, Kojima W, Kimura M, Imai K, Udagawa C, Motono C, Hirokawa T, Tashiro S, Caaveiro JMM, Tsumoto K, Yamano K, Tanaka K, and Matsuda N
- Subjects
- Humans, Mitochondria genetics, Parkinson Disease genetics
- Abstract
Diverse genes associated with familial Parkinson's disease (familial Parkinsonism) have been implicated in mitochondrial quality control. One such gene, PARK7 encodes the protein DJ-1, pathogenic mutations of which trigger its translocation from the cytosol to the mitochondrial matrix. The translocation of steady-state cytosolic proteins like DJ-1 to the mitochondrial matrix upon missense mutations is rare, and the underlying mechanism remains to be elucidated. Here, we show that the protein unfolding associated with various DJ-1 mutations drives its import into the mitochondrial matrix. Increasing the structural stability of these DJ-1 mutants restores cytosolic localization. Mechanistically, we show that a reduction in the structural stability of DJ-1 exposes a cryptic N-terminal mitochondrial-targeting signal (MTS), including Leu10, which promotes DJ-1 import into the mitochondrial matrix for subsequent degradation. Our work describes a novel cellular mechanism for targeting a destabilized cytosolic protein to the mitochondria for degradation., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)
- Published
- 2021
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10. Phenotypic and Genetic Characterization for Incompatible Cross-Match Cases in the Feline AB Blood Group System.
- Author
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Uno Y, Yaguchi M, Kobayashi T, Onozawa E, Ochiai K, Yoshida K, Nakamura C, Udagawa C, and Omi T
- Abstract
The feline AB blood group system (blood types A, B, and AB) encoding the cytidine monophosphate-N-acetylneuraminic acid hydroxylase ( CMAH ) gene is the most significant in transfusion medicine and hemolysis of the newborn for cats. Blood typing and cross-matching in pre-transfusion testing are crucial to determining blood compatibility and thus prevent hemolytic transfusion reactions. We here performed serological and genetic investigations to characterize blood samples from cats with discordant results for card agglutination (CARD) and the alloantibody agglutination test for blood typing in two cats (subjects K and R). Subject K showed incompatible cross-matching in pre-transfusion testing. Red blood cells from subjects K and R determined blood type B from the CARD method showed blood type AB by alloanti-A and alloanti-B antibodies in agglutination testing. Genomic DNA sequencing of the coding region (exons 1a to 14) for the cat CMAH gene showed that subject K had four mutations with heterozygosity at c.139C>T, c.179G>T, c.327A>C, and c.364C>T. Similarly, the CMAH gene of subject R carried six mutations with heterozygosity at c.142G>A, c.187A>G, c.268T>A, c.327A>C, c.773G>A and c.1603G>A, representing a new diplotype including a novel synonymous single nucleotide polymorphism (SNP) in exon 7 (c.773 G>A: Arg258Gln). The CMAH diplotype in subjects K and R was different from major diplotype in blood type B cats. This study is the first to report CMAH variants in cats with discordant blood types between CARD and TUBE methods. These results could assist in the classification of feline AB blood types for transfusion medicine to avoid blood incompatibilities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Uno, Yaguchi, Kobayashi, Onozawa, Ochiai, Yoshida, Nakamura, Udagawa and Omi.)
- Published
- 2021
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11. Modulation of TNFR 1-triggered two opposing signals for inflammation and apoptosis via RIPK 1 disruption by geldanamycin in rheumatoid arthritis.
- Author
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Saeki Y, Okita Y, Igashira-Oguro E, Udagawa C, Murata A, Tanaka T, Mukai J, Miyazawa K, Hoshida Y, and Ohshima S
- Subjects
- Animals, Benzoquinones, Humans, Inflammation drug therapy, Lactams, Macrocyclic, Mice, NF-kappa B, Tumor Necrosis Factor-alpha, Apoptosis, Arthritis, Rheumatoid drug therapy
- Abstract
Objectives: To evaluate the ability of geldanamycin to modulate two opposing TNFα/TNFR1-triggered signals for inflammation and cell death., Methods: The effects of geldanamycin on TNFα-induced proinflammatory cytokine production, apoptosis, NF-κB activation, caspase activation, and necroptosis in a human rheumatoid synovial cell line (MH7A) were evaluated via ELISA/qPCR, flow cytometry, dual-luciferase reporter assay, and western blotting assay, respectively. In addition, therapeutic effects on murine collagen-induced arthritis (CIA) were also evaluated., Results: Geldanamycin disrupted RIPK1 in MH7A, thereby inhibiting TNFα-induced proinflammatory cytokine production and enhancing apoptosis. TNFα-induced NF-κB and MLKL activation was inhibited, whereas caspase 8 activation was enhanced. Recombinant RIPK1 restored the geldanamycin-mediated inhibition of TNFα-induced NF-κB activation. In addition, GM showed more clinical effectiveness than a conventional biologic TNF inhibitor, etanercept, in murine CIA and significantly attenuated synovial hyperplasia, a histopathological hallmark of RA., Conclusions: GM disrupts RIPK1 and selectively inhibits the TNFR1-triggered NF-κB activation signaling pathway, while enhancing the apoptosis signaling pathway upon TNFα stimulation, thereby redressing the balance between these two opposing signals in a human rheumatoid synovial cell line. Therapeutic targeting RIPK1 may be a novel concept which involves TNF inhibitor acting as a TNFR1-signal modulator and have great potential for a more fundamental, effective, and safer TNF inhibitor. Key Points • Geldanamycin (GM) disrupts RIPK1 and selectively inhibits the TNFR1-triggered NF-κB activation signaling pathway while enhancing the apoptosis signaling pathway upon TNFα stimulation, thereby redressing the balance between these two opposing signals in a human rheumatoid synovial cell line, MH7A. • GM showed more clinical effectiveness than a conventional biologic TNF-inhibitor, etanercept, in murine collagen-induced arthritis (CIA), and significantly attenuated synovial hyperplasia, a histopathological hallmark of RA. • Therapeutic targeting RIPK1 may be a novel concept which involves TNF inhibitor acting as a TNFR1-signal modulator and have great potential for a more fundamental, effective, and safer TNF-inhibitor.
- Published
- 2021
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12. Pharmacogenetics for severe adverse drug reactions induced by molecular-targeted therapy.
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Udagawa C and Zembutsu H
- Subjects
- Genetic Variation genetics, Humans, Pharmacogenetics methods, Drug-Related Side Effects and Adverse Reactions genetics, Molecular Targeted Therapy adverse effects
- Abstract
Molecular-targeted drugs specifically interfere with molecules that are frequently overexpressed or mutated in cancer cells. As such, these drugs are generally considered to precisely attack cancer cells, thereby inducing fewer adverse drug reactions (ADRs). However, molecular-targeted drugs can still cause characteristic ADRs that, although rarely severe, can be life-threatening. Therefore, it is becoming increasingly important to be able to predict which patients are at risk of developing ADRs after treatment with molecular-targeted therapy. The emerging field of pharmacogenetics aims to better distinguish the genetic variants associated with drug toxicity and efficacy to improve the selection of therapeutic strategies for each genetic profile. Here, we provide an overview of the current reports on the relationship between genetic variants and molecular-targeted drug-induced severe ADRs in oncology., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
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- 2020
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13. Whole-exome sequencing of 79 xenografts as a potential approach for the identification of genetic variants associated with sensitivity to cytotoxic anticancer drugs.
- Author
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Udagawa C, Sasaki Y, Tanizawa Y, Suemizu H, Ohnishi Y, Nakamura Y, Tokino T, and Zembutsu H
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- Animals, Antineoplastic Agents pharmacology, Cytotoxins pharmacology, Heterografts, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasms pathology, Treatment Outcome, Exome Sequencing, Antineoplastic Agents therapeutic use, Cytotoxins therapeutic use, Drug Resistance, Neoplasm drug effects, Genetic Variation, Neoplasms drug therapy, Neoplasms genetics, Xenograft Model Antitumor Assays methods
- Abstract
Chemotherapy response remains unpredictable in most patients with cancer. In this study, we performed whole-exome sequencing of 79 cancer xenografts derived from human cancer tissues to identify genetic predictors of chemosensitivity to nine cytotoxic anticancer drugs. Xenografts were harvested from 12 organs with cancer and implanted into nude mice. The mice were exposed to one of nine cytotoxic anticancer drugs (5-fluorouracil, nimustine, adriamycin, cyclophosphamide, cisplatin, mitomycin C, methotrexate, vincristine, and vinblastine) to assess the correlation between chemosensitivity response and variant allele frequency. We found 162 candidate variants that were possibly associated with chemosensitivity to one or more of the nine anticancer drugs (P < 0.01). In a subgroup analysis of breast and gastric cancer xenografts, 78 and 67 variants, respectively, were possibly associated with chemosensitivity. This approach may help to contribute to the development of personalized treatments that may allow for the prescription of optimal chemotherapy regimens among patients with cancer., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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14. Lack of association between a disease-susceptible single-nucleotide polymorphism, rs2230926 of TNFAIP3 , and tumour necrosis factor inhibitor therapeutic failure in Japanese patients with rheumatoid arthritis.
- Author
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Matsuoka H, Kabata D, Taura A, Matsui T, Takahi K, Hirano F, Katayama M, Okamoto A, Suenaga Y, Suematsu E, Yoshizawa S, Ohmura K, Ito S, Takaoka H, Oguro E, Kuzuya K, Okita Y, Udagawa C, Yoshimura M, Teshigawara S, Harada Y, Isoda K, Yoshida Y, Ohshima S, Tohma S, and Saeki Y
- Subjects
- Adalimumab therapeutic use, Adult, Aged, Antibodies, Monoclonal therapeutic use, Arthritis, Rheumatoid genetics, Asian People, Etanercept therapeutic use, Female, Humans, Infliximab therapeutic use, Japan, Male, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Treatment Failure, Arthritis, Rheumatoid drug therapy, Tumor Necrosis Factor Inhibitors therapeutic use, Tumor Necrosis Factor alpha-Induced Protein 3 genetics
- Published
- 2020
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15. Liquid biopsy for the detection of clinical biomarkers in early breast cancer: new insights and challenges.
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Matsutani A, Udagawa C, Matsunaga Y, Nakamura S, and Zembutsu H
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- Breast Neoplasms blood, Clinical Trials as Topic, Female, Humans, Liquid Biopsy, Biomarkers, Tumor blood, Breast Neoplasms pathology, Circulating Tumor DNA blood, Early Detection of Cancer methods
- Abstract
The widespread use of breast screening programs has contributed to the detection of early stage breast cancer, which is often asymptomatic. Early diagnosis is essential to avoid overtreatment and improve clinical outcomes, as early stage breast cancer is rarely life-threatening if detected quickly. Despite this, tissue biopsy remains the principle method for detecting these cancers. Liquid biopsy has been recently proposed as a promising detection method in oncology that is not only less invasive but also contributes to the early diagnosis of breast cancer. Here, we describe the clinical utility of liquid biopsy as a tool for the early detection of breast cancer.
- Published
- 2020
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16. Concentrations of 137 Cs radiocaesium in the organs and tissues of low-dose-exposed wild Japanese monkeys.
- Author
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Omi T, Nakiri S, Nakanishi S, Ishii N, Uno T, Konno F, Inagaki T, Sakamoto A, Shito M, Udagawa C, Tada N, Ochiai K, Kato T, Kawamoto Y, Tsuchida S, and Hayama SI
- Subjects
- Air Pollutants, Radioactive analysis, Air Pollutants, Radioactive metabolism, Air Pollutants, Radioactive pharmacokinetics, Animals, Cesium Radioisotopes analysis, Cesium Radioisotopes metabolism, Earthquakes, Fukushima Nuclear Accident, Japan, Lung metabolism, Macaca fuscata, Radiation Exposure analysis, Spleen metabolism, Tissue Distribution, Brain metabolism, Cesium Radioisotopes pharmacokinetics, Kidney metabolism, Liver metabolism, Muscles metabolism, Myocardium metabolism
- Abstract
Objectives: Following the massive earthquake that struck eastern Japan on March 11, 2011, a large amount of radioactive material was released into the environment from the damaged reactor of the Fukushima Daiichi Nuclear Power Plant (FDNPP). After the FDNPP accident, radiocaesium was first detected in muscle samples from wild Japanese monkeys exposed to radioactive materials, and haematologic effects, changes in head size, and delayed body weight gain were also reported, but little is known about the distribution of
137 Cs in the organs and tissues of wild Japanese monkeys., Results: We detected the137 Cs in various organ and tissue samples of 10 wild Japanese monkeys inhabiting the forested areas of Fukushima City that were captured between July and August 2012. Among muscle, brain, heart, kidney, liver, lung, and spleen, muscle exhibited the highest and the brain the lowest137 Cs concentration. The concentration (mean ± SD) of137 Cs in muscle, brain, heart, kidney, liver, lung, and spleen was 77 ± 66, 26 ± 22, 41 ± 35, 49 ± 41, 41 ± 38, 53 ± 41, and 53 ± 51 Bq/kg, respectively. These results can help us understand the biological effects of long-term internal radiation exposure in non-human primates.- Published
- 2020
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17. A Genome-Wide Association Study Identifies Five Novel Genetic Markers for Trastuzumab-Induced Cardiotoxicity in Japanese Population.
- Author
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Nakano MH, Udagawa C, Shimo A, Kojima Y, Yoshie R, Zaha H, Abe N, Motonari T, Unesoko M, Tamura K, Shimoi T, Yoshida M, Yoshida T, Sakamoto H, Kato K, Mushiroda T, Tsugawa K, and Zembutsu H
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Genes, erbB-2, Genetic Loci genetics, Genetic Markers, Genome-Wide Association Study, Genotype, Heart Diseases chemically induced, Heart Diseases genetics, Humans, Japan, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Trastuzumab pharmacology, Breast Neoplasms complications, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Cardiotoxicity etiology, Cardiotoxicity genetics, Trastuzumab adverse effects
- Abstract
Trastuzumab has been administered to patients with human epidermal growth factor receptor 2 (HER2)-positive cancer, however, the cardiotoxicity is identified as one of the life-threatening toxicities. Clinically useful biomarker for trastuzumab-induced cardiotoxicity has been expected to be developed. To identify a novel genetic marker(s) determining the risk of trastuzumab-induced cardiotoxicity, we performed a first genome-wide association study (GWAS) in Japanese population. We enrolled 481 patients who had been treated with trastuzumab and carried out a GWAS using 11 cases (with cardiotoxicity) and 257 controls (without cardiotoxicity). Top 100 single nucleotide polymorphisms (SNPs) which revealed the smallest p values in GWAS (p = 7.60 × 10
-7 - 2.01 × 10-4 ) were further examined using replication samples consisted of 14 cases and 199 controls. The combined analysis of the GWAS and replication study indicated possible association of five loci with trastuzumab-induced cardiotoxicity (rs9316695 on chromosome 13q14.3, rs28415722 on chromosome 15q26.3, rs7406710 on chromosome 17q25.3, rs11932853 on chromosome 4q25, and rs8032978 on chromosome 15q26.3, Pcombined = 6.00 × 10-6 , 8.88 × 10-5 , 1.07 × 10-4 , 1.42 × 10-4 , 1.60 × 10-4 , respectively). Furthermore, we developed a risk prediction model for trastuzumab-induced cardiotoxicity using the five marker SNPs. The incidence of trastuzumab-induced cardiotoxicity in patients with risk score ≥5 was significantly higher (42.5%) compared to that in patients with score ≤ 4 (1.8%) (p = 7.82 × 10-15 , odds ratio = 40.0). These findings suggest the potential to improve the ability of physicians to avoid the trastuzumab-induced cardiotoxicity for patients with HER2-positive cancer.- Published
- 2019
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18. Whole genome sequencing to identify predictive markers for the risk of drug-induced interstitial lung disease.
- Author
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Udagawa C, Horinouchi H, Shiraishi K, Kohno T, Okusaka T, Ueno H, Tamura K, Ohe Y, and Zembutsu H
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Case-Control Studies, Female, Humans, Male, Middle Aged, Mutation, Neoplasms drug therapy, Polymorphism, Single Nucleotide, Prognosis, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Whole Genome Sequencing, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers, Genetic Predisposition to Disease, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial etiology, Neoplasms complications
- Abstract
Drug-induced interstitial lung disease (DIILD) is a serious side effect of chemotherapy in cancer patients with an extremely high mortality rate. In this study, to identify genetic variants with greater risk of DIILD, we carried out whole genome sequencing (WGS) of germline DNA samples from 26 patients who developed DIILD, and conducted a case-control association study between these 26 cases and general Japanese population controls registered in the integrative Japanese Genome Variation Database (iJGVD) as a screening study. The associations of 42 single nucleotide variants (SNVs) showing P < 0.0001 were further validated using an independent cohort of 18 DIILD cases as a replication study. A further combined analysis of the screening and replication studies showed a possible association of two SNVs, rs35198919 in intron 1 of the chromosome 22 open reading frame 34 (C22orf34) and rs12625311 in intron 1 of the teashirt zinc finger homeobox 2 (TSHZ2), with DIILD (Pcombined = 1.87 × 10-5 and 5.16 × 10-5, respectively). Furthermore, in a subgroup analysis of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-induced interstitial lung disease (ILD), we observed seven candidate SNVs that were possibly associated with ILD (P < 0.00001). This is the first study to identify genetic markers for the risk of DIILD using WGS. Collectively, our novel findings indicate that these SNVs may be applicable for predicting the risk of DIILD in patients receiving chemotherapy., Competing Interests: Hitoshi Zembutsu received research funding from AstraZeneca as we described in the online submission form and had no other relationship with them or others. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
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19. Crosstalk between tumor necrosis factor-alpha signaling and aryl hydrocarbon receptor signaling in nuclear factor -kappa B activation: A possible molecular mechanism underlying the reduced efficacy of TNF-inhibitors in rheumatoid arthritis by smoking.
- Author
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Nii T, Kuzuya K, Kabata D, Matsui T, Murata A, Ohya T, Matsuoka H, Shimizu T, Oguro E, Okita Y, Udagawa C, Yoshimura M, Kudo-Tanaka E, Teshigawara S, Harada Y, Yoshida Y, Isoda K, Tsuji SI, Ohshima S, Hashimoto J, Shintani A, Takehana Y, Tohma S, and Saeki Y
- Subjects
- Aged, Arthritis, Rheumatoid epidemiology, Cells, Cultured, Cigarette Smoking adverse effects, Drug Resistance, Humans, Japan epidemiology, Lymphocyte Activation, Male, Middle Aged, NF-kappa B genetics, Receptor Cross-Talk, Signal Transduction, Transcriptional Activation, Treatment Outcome, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Infliximab therapeutic use, NF-kappa B metabolism, Protein Kinase Inhibitors therapeutic use, Receptors, Aryl Hydrocarbon metabolism, Registries, T-Lymphocytes immunology, Tumor Necrosis Factor-alpha metabolism, Withholding Treatment statistics & numerical data
- Abstract
Objectives: To examine the influence of smoking on biologics treatment against different therapeutic targets, such as TNFα, IL-6, and T cell, in rheumatoid arthritis (RA) and elucidate the underlying molecular mechanism., Methods: The association between drug-discontinuation due to poor therapeutic response and smoking status was analyzed individually in biologics against different therapeutic targets by a multivariable logistic regression analysis using the "NinJa" Registry, one of the largest cohorts of Japanese RA patients. In vitro enhancement of TNFα-induced NF-κB activation and subsequent proinflammatory cytokine production by cigarette chemical components was examined by RT-PCR, qPCR, ELISA, and western blotting using an immortalized rheumatoid synovial cell line, MH7A., Results: The rate of drug-discontinuation due to poor therapeutic response was higher in the current smoking group than in the never- or ever-smoking groups (the odds ratio of current/never smoking: 2.189, 95%CI; 1.305-3.672,P = 0.003; current/ever: 1.580, 95%CI; 0.879-2.839,P = 0.126) in the TNF inhibitor (TNFi) treatment group. However, this tendency was not observed in either the IL-6 or T cell inhibitor treatment groups. Cigarette smoke chemical components, such as benzo[α]pyrene, known as aryl hydrocarbon receptor (AhR) ligands, themselves activated NF-κB and induced proinflammatory cytokines, IL-1β and IL-6. Furthermore, they also significantly enhanced TNFα-induced NF-κB activation and proinflammatory cytokine production. This enhancement was dominantly inhibited by Bay 11-7082, an NF-κB inhibitor., Conclusions: These results suggest a crosstalk between TNFα signaling and AhR signaling in NF-κB activation which may constitute one of the molecular mechanisms underlying the higher incidence of drug-discontinuation in RA patients undergoing TNFi treatment with smoking habits., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2019
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20. A genome-wide association study identifies three novel genetic markers for response to tamoxifen: A prospective multicenter study.
- Author
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Onishi H, Udagawa C, Kubo M, Nakamura S, Akashi-Tanaka S, Kuwayama T, Watanabe C, Takamaru T, Takei H, Ishikawa T, Miyahara K, Matsumoto H, Hasegawa Y, Momozawa Y, Low SK, Kutomi G, Shima H, Satomi F, Okazaki M, Zaha H, Onomura M, Matsukata A, Sagara Y, Baba S, Yamada A, Shimada K, Shimizu D, Tsugawa K, Shimo A, Hartman M, Chan CW, Lee SC, Endo I, and Zembutsu H
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms surgery, Chromosomes, Human genetics, Female, Humans, Ki-67 Antigen metabolism, Middle Aged, Preoperative Care, Prospective Studies, Receptor, ErbB-2 metabolism, Sequence Analysis, DNA, Tamoxifen pharmacology, Treatment Outcome, Breast Neoplasms drug therapy, Genetic Markers drug effects, Genome-Wide Association Study methods, Polymorphism, Single Nucleotide, Tamoxifen therapeutic use
- Abstract
Purpose: Although association studies of genetic variations with the clinical outcomes of breast cancer patients treated with tamoxifen have been reported, genetic factors which could determine individual response to tamoxifen are not fully clarified. We performed a genome-wide association study (GWAS) to identify novel genetic markers for response to tamoxifen., Experimental Design: We prospectively collected 347 blood samples from patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. We used Ki-67 response in breast cancer tissues after preoperative short-term tamoxifen therapy as a surrogate marker for response to tamoxifen. We performed GWAS and genotype imputation using 275 patients, and an independent set of 72 patients was used for replication study., Results: The combined result of GWAS and the replication study, and subsequent imputation analysis indicated possible association of three loci with Ki-67 response after tamoxifen therapy (rs17198973 on chromosome 4q34.3, rs4577773 on 6q12, and rs7087428 on 10p13, Pcombined = 5.69 x 10-6, 1.64 x 10-5, and 9.77 x 10-6, respectively). When patients were classified into three groups by the scoring system based on the genotypes of the three SNPs, patients with higher scores showed significantly higher after/before ratio of Ki-67 compared to those with lower scores (P = 1.8 x 10-12), suggesting the cumulative effect of the three SNPs., Conclusion: We identified three novel loci, which could be associated with clinical response to tamoxifen. These findings provide new insights into personalized hormonal therapy for the patients with breast cancer., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
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21. Whole exome sequencing to identify genetic markers for trastuzumab-induced cardiotoxicity.
- Author
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Udagawa C, Nakamura H, Ohnishi H, Tamura K, Shimoi T, Yoshida M, Yoshida T, Totoki Y, Shibata T, and Zembutsu H
- Subjects
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Eye Proteins genetics, Female, Germ-Line Mutation, Humans, Keratin-15 genetics, Male, Middle Aged, Transcription Factors genetics, Ubiquitin-Protein Ligases genetics, Cardiotoxicity genetics, Genetic Markers genetics, Polymorphism, Single Nucleotide, Trastuzumab toxicity, Exome Sequencing methods
- Abstract
Although trastuzumab-induced cardiotoxicity is an important determinant to limit the use of this drug, the molecular mechanism of risk for this toxicity is not well understood. To identify genetic variants determining the risk of trastuzumab-induced cardiotoxicity, we carried out whole exome sequencing of germline DNA samples from 9 patients with trastuzumab-induced cardiotoxicity, and conducted a case-control association study of 2258 genetic variants between 9 cases (with trastuzumab-induced cardiotoxicity) and general Japanese population controls registered in the Human Genetic Variation Database (HGVD). The top variant which showed the lowest P-value in the screening study was rs139503277 in PHD Finger Protein 3 (P
min = .00012, odds ratio [OR] = 51.23). To further validate the result of screening study, we carried out a replication study of 10 variants showing Pmin < .001 in the screening study using 234 independent patients treated with trastuzumab, including 10 cases and 224 controls (without trastuzumab-induced cardiotoxicity). In the replication study, we observed that three variants had an effect in the same direction as in the screening study (rs78272919 in exon 2 of Keratin 15, rs5762940 in exon 2 of zinc and ring finger 3, and rs139944387 in exon 44 of Eyes shut homologs [EYS]). A combined result of the screening and the replication studies suggested an association of a locus on chromosome 6q12 with trastuzumab-induced cardiotoxicity (rs139944387 in EYS, combined Pmin = .00056, OR = 13.73). This finding provides new insights into personalized trastuzumab therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive cancer., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)- Published
- 2018
- Full Text
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22. Targeted sequencing reveals genetic variants associated with sensitivity of 79 human cancer xenografts to anticancer drugs.
- Author
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Udagawa C, Sasaki Y, Suemizu H, Ohnishi Y, Ohnishi H, Tokino T, and Zembutsu H
- Abstract
Although there has been progress moving from a 'one-size-fits-all' cytotoxic approach to personalized molecular medicine, the majority of patients with cancer receive chemotherapy using cytotoxic anticancer drugs. The sequencing analysis of 409 genes associated with cancer was conducted in the present study using 59 DNA sequences extracted from human cancer xenografts implanted into nude mice, of which sensitivity to 9 cytotoxic anticancer drugs [5-fluorouracil, nimustine, adriamycin, cyclophosphamide, cisplatin, mitomycin C (MMC), methotrexate, vincristine (VCR), and vinblastine] was examined. The present study investigated the association between the sensitivities of the xenografts to the 9 anticancer drugs and the frequency of single nucleotide variants (SNV). The correlation between the expression level of the genes and sensitivities to the 9 drugs in the above xenografts was also estimated. In the screening study using 59 xenografts, 3 SNVs (rs1805321, rs62456182 in PMS1 Homolog 2, Mismatch Repair System Component and rs13382825 in LDL Receptor Related Protein 1B), were associated with sensitivity to VCR and MMC, respectively (P<0.001). A replication study of 596 SNVs was subsequently performed, which indicated P<0.05 in the screening study using independent samples of 20 xenografts. A combined result of the screening and replication studies indicated that 35 SNVs were potentially associated with sensitivities to one or more of the nine anticancer drugs (P
combined =0.0011-0.035). Of the 35 SNVs, rs16903989 and rs201432181 in Leukemia Inhibitory Factor Receptor α and Adhesion G Protein-Coupled Receptor A2 were commonly associated with sensitivity to 2 or 4 anticancer drugs, respectively. These findings provide novel insights which may benefit the development of personalized anticancer therapy for patients with cancer in the future.- Published
- 2018
- Full Text
- View/download PDF
23. Enzymatic mechanisms of biological magnetic sensitivity.
- Author
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Letuta UG, Berdinskiy VL, Udagawa C, and Tanimoto Y
- Subjects
- Escherichia coli cytology, Intracellular Space enzymology, Quantum Theory, Escherichia coli enzymology, Magnetic Fields
- Abstract
Primary biological magnetoreceptors in living organisms is one of the main research problems in magnetobiology. Intracellular enzymatic reactions accompanied by electron transfer have been shown to be receptors of magnetic fields, and spin-dependent ion-radical processes can be a universal mechanism of biological magnetosensitivity. Magnetic interactions in intermediate ion-radical pairs, such as Zeeman and hyperfine (HFI) interactions, in accordance with proposed strict quantum mechanical theory, can determine magnetic-field dependencies of reactions that produce biologically important molecules needed for cell growth. Hyperfine interactions of electrons with nuclear magnetic moments of magnetic isotopes can explain the most important part of biomagnetic sensitivities in a weak magnetic field comparable to the Earth's magnetic field. The theoretical results mean that magnetic-field dependencies of enzymatic reaction rates in a weak magnetic field that can be independent of HFI constant a, if H << a, and are determined by the rate constant of chemical transformations in the enzyme active site. Both Zeeman and HFI interactions predict strong magnetic-field dependence in weak magnetic fields and magnetic-field independence of enzymatic reaction rate constants in strong magnetic fields. The theoretical results can explain the magnetic sensitivity of E. coli cell and demonstrate that intracellular enzymatic reactions are primary magnetoreceptors in living organisms. Bioelectromagnetics. 38:511-521, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
- Full Text
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24. Molecular Characterization of the Cytidine Monophosphate-N-Acetylneuraminic Acid Hydroxylase (CMAH) Gene Associated with the Feline AB Blood Group System.
- Author
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Omi T, Nakazawa S, Udagawa C, Tada N, Ochiai K, Chong YH, Kato Y, Mitsui H, Gin A, Oda H, Azakami D, Tamura K, Sako T, Inagaki T, Sakamoto A, Tsutsui T, Bonkobara M, Tsuchida S, and Ikemoto S
- Subjects
- Alleles, Animals, Blood Group Antigens genetics, Blood Group Antigens immunology, Cats, Erythrocytes metabolism, Exons, Genetic Loci, Haplotypes, Mixed Function Oxygenases chemistry, Mixed Function Oxygenases metabolism, N-Acetylneuraminic Acid metabolism, Neuraminic Acids metabolism, Polymorphism, Single Nucleotide, RNA, Messenger metabolism, Sequence Analysis, DNA, Blood Group Antigens metabolism, Mixed Function Oxygenases genetics
- Abstract
Cat's AB blood group system (blood types A, B, and AB) is of major importance in feline transfusion medicine. Type A and type B antigens are Neu5Gc and Neu5Ac, respectively, and the enzyme CMAH participating in the synthesis of Neu5Gc from Neu5Ac is associated with this cat blood group system. Rare type AB erythrocytes express both Neu5Gc and Neu5Ac. Cat serum contains naturally occurring antibodies against antigens occurring in the other blood types. To understand the molecular genetic basis of this blood group system, we investigated the distribution of AB blood group antigens, CMAH gene structure, mutation, diplotypes, and haplotypes of the cat CMAH genes. Blood-typing revealed that 734 of the cats analyzed type A (95.1%), 38 cats were type B (4.9%), and none were type AB. A family of three Ragdoll cats including two type AB cats and one type A was also used in this study. CMAH sequence analyses showed that the CMAH protein was generated from two mRNA isoforms differing in exon 1. Analyses of the nucleotide sequences of the 16 exons including the coding region of CMAH examined in the 34 type B cats and in the family of type AB cats carried the CMAH variants, and revealed multiple novel diplotypes comprising several polymorphisms. Haplotype inference, which was focused on non-synonymous SNPs revealed that eight haplotypes carried one to four mutations in CMAH, and all cats with type B (n = 34) and AB (n = 2) blood carried two alleles derived from the mutated CMAH gene. These results suggested that double haploids selected from multiple recessive alleles in the cat CMAH loci were highly associated with the expression of the Neu5Ac on erythrocyte membrane in types B and AB of the feline AB blood group system., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
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25. Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity.
- Author
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Ochiai K, Morimatsu M, Kato Y, Ishiguro-Oonuma T, Udagawa C, Rungsuriyawiboon O, Azakami D, Michishita M, Ariyoshi Y, Ueki H, Nasu Y, Kumon H, Watanabe M, and Omi T
- Subjects
- Adaptor Proteins, Signal Transducing, Adenocarcinoma genetics, Adenocarcinoma pathology, Apoptosis, Blotting, Western, Carrier Proteins genetics, Cell Proliferation, Chemokines, Humans, Intercellular Signaling Peptides and Proteins genetics, Male, Molecular Chaperones, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Protein Interaction Maps, Protein Multimerization, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Receptors, Androgen genetics, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Two-Hybrid System Techniques, Adenocarcinoma metabolism, Carrier Proteins metabolism, Intercellular Signaling Peptides and Proteins metabolism, Prostatic Neoplasms metabolism, Receptors, Androgen metabolism
- Abstract
REIC/DKK-3 is a tumor suppressor, however, its intracellular physiological functions and interacting molecules have not been fully clarified. Using yeast two-hybrid screening, we found that small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, is a novel interacting partner of REIC/DKK-3. Mammalian two-hybrid and pull-down assay results indicated that the SGTA-REIC/DKK-3 interaction involved the N-terminal regions of both REIC/DKK-3 and SGTA and that REIC/DKK-3 interfered with the dimerization of SGTA, which is a component of the AR complex and a suppressor of dynein motor-dependent AR transport and signaling. A reporter assay in human prostate cancer cells that displayed suppressed AR signaling by SGTA showed recovery of AR signaling by REIC/DKK-3 expression. Considering these results and our previous data that REIC/DKK-3 interacts with the dynein light chain TCTEX-1, we propose that the REIC/DKK-3 protein interferes with SGTA dimerization, promotes dynein-dependent AR transport and then upregulates AR signaling.
- Published
- 2016
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26. Polymorphisms of canine BRCA2 BRC repeats affecting interaction with RAD51.
- Author
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Ochiai K, Ishiguro-Oonuma T, Yoshikawa Y, Udagawa C, Kato Y, Watanabe M, Bonkobara M, Morimatsu M, and Omi T
- Subjects
- Animals, BRCA2 Protein metabolism, Dogs, Gene Frequency, Genes, BRCA2, Genetic Association Studies, HEK293 Cells, Humans, Polymorphism, Genetic, Protein Binding, BRCA2 Protein genetics, Rad51 Recombinase metabolism
- Abstract
Mutations in the breast cancer susceptibility gene BRCA2 leading to the failure of interactions with the recombinase RAD51 are associated with an increased risk of cancer in humans. This interaction depends on the eight BRC repeat (BRC1-8) sequences in BRCA2. We previously reported that canine BRC3 has two polymorphisms (T1425P and K1435R) influencing the interaction with RAD51, and 1435R was identified in mammary tumor dog samples. In this study, we investigated the sequence variations of BRC3 and 4 in 236 dogs of five breeds. Allele frequencies of 1425P and 1435R were 0.063 and 0.314, respectively, and there was no other polymorphism in the sequenced region. A mammalian two-hybrid assay using BRC3-4 sequences demonstrated that 1425P allele reduced the binding strength with RAD51 but 1435R had no effect. These results may provide an insight into the functions of not only individual but also multiple BRC repeats of BRCA2 in dogs.
- Published
- 2015
- Full Text
- View/download PDF
27. The genetic association study between polymorphisms in uncoupling protein 2 and uncoupling protein 3 and metabolic data in dogs.
- Author
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Udagawa C, Tada N, Asano J, Ishioka K, Ochiai K, Bonkobara M, Tsuchida S, and Omi T
- Subjects
- Animals, Blood Glucose metabolism, Breeding, Cholesterol blood, Dogs, Exons, Female, Gene Expression, Hypercholesterolemia blood, Introns, Ion Channels blood, L-Lactate Dehydrogenase blood, Male, Mitochondrial Proteins blood, Triglycerides blood, Uncoupling Protein 2, Uncoupling Protein 3, Genetic Association Studies, Hypercholesterolemia genetics, INDEL Mutation, Ion Channels genetics, Mitochondrial Proteins genetics, Polymorphism, Single Nucleotide
- Abstract
Background: The uncoupling proteins (UCPs) in the mitochondrial inner membrane are members of the mitochondrial anion carrier protein family that play an important role in energy homeostasis. Genetic association studies have shown that human UCP2 and UCP3 variants (SNPs and indels) are associated with obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. The aim of this study was to examine the genetic association between polymorphisms in UCP2 and UCP3 and metabolic data in dogs., Results: We identified 10 SNPs (9 intronic and 1 exonic) and 4 indels (intronic) in UCP2, and 13 SNPs (11 intronic and 2 exonic) and one indel (exonic) in UCP3, by DNA sequence analysis of 11 different dog breeds (n=119). An association study between these UCP2 and UCP3 variants and the biochemical parameters of glucose, total cholesterol, lactate dehydrogenase and triglyceride in Labrador Retrievers (n=50) showed that none of the UCP2 polymorphisms were significantly associated with the levels of these parameters. However, four UCP3 SNPs (intron 1) were significantly associated with total cholesterol levels. In addition, the allele frequencies of two of the four SNPs associated with higher total cholesterol levels in a breed that is susceptible to hypercholesterolemia (Shetland Sheepdogs, n=30), compared with the control breed (Shiba, n=30)., Conclusion: The results obtained from a limited number of individuals suggest that the UCP3 gene in dogs may be associated with total cholesterol levels. The examination of larger sample sizes and further analysis will lead to increased precision of these results.
- Published
- 2014
- Full Text
- View/download PDF
28. Massive thrombus in the left ventricle: a case report.
- Author
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Udagawa C, Akima T, Horiuchi F, Nishida M, Tachikawa K, Izawa M, Kanki H, and Murayama A
- Published
- 2014
- Full Text
- View/download PDF
29. Magnetic field effects on copper metal deposition from copper sulfate aqueous solution.
- Author
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Udagawa C, Maeda A, Katsuki A, Maki S, Morimoto S, and Tanimoto Y
- Subjects
- Adsorption, Equipment Design, Magnetic Fields, Magnetics instrumentation, Copper analysis, Copper Sulfate chemistry, Zinc chemistry
- Abstract
Effects of a magnetic field (≤0.5 T) on electroless copper metal deposition from the reaction of a copper sulfate aqueous solution and a zinc thin plate were examined in this study. In a zero field, a smooth copper thin film grew steadily on the plate. In a 0.38 T field, a smooth copper thin film deposited on a zinc plate within about 1 min. Then, it peeled off repeatedly from the plate. The yield of consumed copper ions increased about 2.1 times compared with that in a zero field. Mechanism of this magnetic field effect was discussed in terms of Lorentz force- and magnetic force-induced convection and local volta cell formation.
- Published
- 2014
- Full Text
- View/download PDF
30. Analysis of mitochondrial DNA HVR1 haplotype of pure-bred domestic dogs in Japan.
- Author
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Sugiyama S, Chong YH, Shito M, Kasuga M, Kawakami T, Udagawa C, Aoki H, Bonkobara M, Tsuchida S, Sakamoto A, Okuda H, Nagai A, and Omi T
- Subjects
- Animals, DNA Primers genetics, Genetic Variation, Haplotypes, Japan, Microsatellite Repeats genetics, Polymorphism, Genetic, Sequence Analysis, DNA, Complementarity Determining Regions genetics, DNA, Mitochondrial genetics, Dogs genetics, Forensic Genetics methods
- Abstract
To develop DNA markers for forensic analysis, we examined the hypervariable region 1 (HVR1) sequences of 447 pure-bred domestic dogs (Canis lupus familiaris) that had been bred and raised in Japan. HVR1 is a 660-bp stretch of mitochondrial (mt) DNA. Among the 447 HVR1 sequences examined, we identified 58 haplotypes from 47 single nucleotide polymorphisms (SNPs) and two insertion-deletion (InDel) polymorphisms. The haplotype diversity inferred from inter-breed analysis (N=154, 88 breeds) was 0.929±0.011. Intra-breed analysis showed that the haplotype diversity of Golden Retrievers (N=53), Labrador Retrievers (N=67), Miniature Dachshunds (N=61), Toy Poodles (N=62), and Welsh Corgis (N=50) was 0.624±0.052, 0.722±0.029, 0.922±0.010, 0.877±0.020, and 0.443±0.084, respectively. The results of this genotype analysis were used to construct a dataset consisting of dog mtDNA HVR1 sequences for use in forensic applications in Japan., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
31. Molecular cloning and tumour suppressor function analysis of canine REIC/Dkk-3 in mammary gland tumours.
- Author
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Ochiai K, Watanabe M, Azakami D, Michishita M, Yoshikawa Y, Udagawa C, Metheenukul P, Chahomchuen T, Aoki H, Kumon H, Morimatsu M, and Omi T
- Subjects
- Amino Acid Sequence, Animals, Dog Diseases genetics, Dogs, Female, Mammary Neoplasms, Animal genetics, Molecular Sequence Data, Protein Transport, Tumor Suppressor Proteins genetics, Cloning, Molecular, Dog Diseases metabolism, Gene Expression Regulation, Neoplastic physiology, Mammary Neoplasms, Animal metabolism, Tumor Suppressor Proteins metabolism
- Abstract
REIC/Dkk-3, a member of the human Dickkopf (Dkk) family, plays a role as a suppressor of growth in several human cancers. In this study, the tumour suppression function of canine REIC/Dkk-3 was investigated. The full-length open reading frame of the canine REIC/Dkk-3 homologue was cloned and the tissue distribution of REIC/Dkk-3 mRNA was determined, along with the subcellular localisation of the REIC/Dkk-3 protein in canine cancer cell lines. Expression of REIC/Dkk-3 was lower in mammary gland tumours and in canine mammary carcinoma cell lines than in normal mammary gland tissue. Overexpression of REIC/Dkk-3 induced apoptosis in canine mammary carcinoma cell lines. These results show that expression of REIC/Dkk-3 is downregulated in canine mammary tumours and that one of the functions of this gene is induction of apoptosis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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