研究者データベース
臼井 達哉USUI Tatsuyaウスイ タツヤ
| ■所属部署名 | 農学研究院 動物生命科学部門 | |||
| ■職名 | 准教授 | |||
Last Updated :2025/01/22
業績情報
氏名・連絡先
氏名
ウスイ タツヤ, 臼井 達哉, USUI Tatsuya生年
1985eメールアドレス
fu7085
go.tuat.ac.jp
主たる所属・職名
農学研究院 動物生命科学部門, 准教授
その他の所属
経歴
- スタンフォード大学
医学部
客員教員
自 2015年04月01日, 至 2015年09月30日 - 山口大学
共同獣医学部・獣医毒性学
助教
自 2013年11月01日, 至 2017年08月31日 - 日本学術振興会
特別研究員(PD・農学)
自 2013年04月01日, 至 2013年10月31日 - 日本学術振興会
特別研究員(DC1・農学)
自 2011年04月01日, 至 2013年03月31日
学歴
学位
免許・資格
教育・研究活動状況
- 近年、三次元の上皮組織構造を培養ディッシュ上で再現する方法としてマトリゲル三次元培養法(オルガノイド培養法)が開発されました。オルガノイド培養法によって、様々な組織の上皮細胞を三次元的に長期培養出来ることが示され、がん研究への応用が始まりました。 当研究室では、前立腺がん罹患犬の尿サンプルを用いて前立腺がんオルガノイドを作製する方法を見出し(Usui et al., Cancer Science, 2017)、このオルガノイドが、生体内のがん微小環境を高いレベルで再現できること、免疫不全マウスの体内で腫瘍を再形成すること、抗がん剤および放射線に対する感受性試験への応用が可能であることを明らかにしました。 また、ヒト、がんモデルマウス、犬由来の様々な組織(肺、大腸、前立腺、膀胱、海馬、肝臓)からオルガノイドを作製し、病態解析を行うことで新たながんを含めた様々な病態メカニズム解明や診断マーカーの開発を目指しています。イヌ膀胱がんオルガノイド培養法の確立
研究分野
研究キーワード
研究テーマ
科学研究費助成事業
- 基盤研究(C)
中皮腫克服に向けた戦略：新規早期診断マーカーおよび治療ターゲット分子の探索研究
自 2023年, 至 2023年 - 基盤研究(B)
非アルコール性脂肪性肝疾患肝発がんラットモデルにおける選択的オートファジーの解明
自 2023年, 至 2023年 - 基盤研究（B）
犬固形腫瘍に対する低コストかつレディメイドで適応可能なCAR-T細胞製剤の開発
自 2023年, 至 2023年 - 挑戦的研究（萌芽）
猫マルチオーガンオルガノイドオンチップシステムの確立
自 2022年, 至 2024年 - 基盤研究(C)
中皮腫克服に向けた戦略：新規早期診断マーカーおよび治療ターゲット分子の探索研究
自 2022年, 至 2022年 - 基盤研究(B)
非アルコール性脂肪性肝疾患肝発がんラットモデルにおける選択的オートファジーの解明
自 2022年, 至 2022年 - 基盤研究(C)
中皮腫克服に向けた戦略：新規早期診断マーカーおよび治療ターゲット分子の探索研究
自 2021年, 至 2021年 - 基盤研究(B)
非アルコール性脂肪性肝疾患肝発がんラットモデルにおける選択的オートファジーの解明
自 2021年, 至 2021年 - 基盤研究(B)
尿サンプル由来オルガノイドを用いた多角的な研究:イヌ膀胱がん克服にむけて
自 2020年, 至 2023年 - 基盤研究(C)
中皮腫克服に向けた戦略：新規早期診断マーカーおよび治療ターゲット分子の探索研究
自 2020年, 至 2020年 - 基盤研究(B)
非アルコール性脂肪性肝疾患肝発がんラットモデルにおける選択的オートファジーの解明
自 2020年, 至 2020年 - 基盤研究(C)
音響キャビテーション誘導による空間選択的抗癌剤取り込み技術の研究
自 2018年, 至 2018年 - 若手研究(B)
三次元マウス肺がんモデルを用いたがん・血管内皮連関機構の解明
自 2017年, 至 2018年
論文
- Chemosensitivity of three patient-derived primary cultures of canine pericardial mesothelioma by single-agent and combination treatment
Nabeta, Rina; Kanaya, Ami; Elbadawy, Mohamed; Usui, Tatsuya; Furuya, Tetsuya; Suzuki, Kazuhiko; Uchide, Tsuyoshi
FRONTIERS IN VETERINARY SCIENCE
FRONTIERS MEDIA SA
IntroductionCanine mesothelioma is a rare malignant tumor that mostly affects body cavities, such as the pericardial and pleural cavities. Chemotherapy plays a crucial role in the treatment of canine mesotheliomas. We aimed to compare the antitumor effects of single-agent and combination chemotherapeutic agents on patient-derived primary cultures of canine pericardial mesothelioma established in this study. We planned to generate xenograft models for future studies.Material and methodsEffusion samples were collected from three dogs with histologically diagnosed pericardial mesothelioma and used for primary culture. Cultured cells were characterized by immunostaining for pan-cytokeratin AE1/AE3, vimentin, Wilms' tumor suppressor gene 1 (WT1), and cytokeratin 5 (CK5). To assess the tumorigenic properties of cells in the effusion and generate a xenograft model, the cell suspension was injected into a severe combined immunodeficient (SCID) mouse either subcutaneously (SC) or intraperitoneally (IP). Lastly, chemosensitivity of established primary cultures against four drugs, doxorubicin, vinorelbine, carboplatin, and gemcitabine, by single-agent treatment as well as combination treatment of carboplatin at a fixed concentration, either 10 or 100 mu M, and gemcitabine at different concentrations ranging from 0-1000 mu M was assessed by cell viability assay.ResultsPrimary cultures were successfully generated and characterized by dual positivity for AE1/AE3 and vimentin and positive staining for WT-1 and CK5, confirming the mesothelial origin of the cells. In the xenograft models, SC mouse developed a subcutaneous mass, whereas IP mouse developed multiple intraperitoneal nodules. The masses were histopathologically consistent with mesotheliomas. The chemosensitivity assay revealed that carboplatin had the highest anti-tumor effects among the four tested single-agent treatments. Furthermore, carboplatin at 100 mu M combined with gemcitabine at clinically relevant doses demonstrated the augmented anti-tumor effects compared to single-agent treatment.Discussion and conclusionPrimary cultures and xenograft models generated in this study could be useful tools for in vitro and in vivo studies of canine mesothelioma. Carboplatin is a highly effective chemotherapeutic agent against canine mesothelioma when used as a sole agent and in combination with gemcitabine.
2023年11月02日, 研究論文（学術雑誌）, 共同, 10, DOI(公開)(r-map) - Adipose Stem Cell-Seeded Decellularized Porcine Pericardium: A Promising Functional Biomaterial to Synergistically Restore the Cardiac Functions Post-Myocardial Infarction
El-Husseiny, Hussein M.; Mady, Eman A.; Usui, Tatsuya; Ishihara, Yusuke; Yoshida, Toshinori; Kobayashi, Mio; Sasaki, Kenta; Ma, Danfu; Yairo, Akira; Mandour, Ahmed S.; Hendawy, Hanan; Doghish, Ahmed S.; Mohammed, Osama A.; Takahashi, Ken; Tanaka, Ryou
VETERINARY SCIENCES
MDPI
Myocardial infarction (MI) is a serious cardiovascular disease as the leading cause of death globally. Hence, reconstruction of the cardiac tissue comes at the forefront of strategies adopted to restore heart functions following MI. In this investigation, we studied the capacity of rat adipose-derived mesenchymal stem cells (r-AdMSCs) and decellularized porcine pericardium (DPP) to restore heart functions in MI animals. MI was induced in four different groups, three of which were treated either using DPP (MI-DPP group), stem cells (MI-SC group), or both (MI-SC/DPP group). Cardiac functions of these groups and the Sham group were evaluated using echocardiography, the intraventricular pressure gradient (IVPG) on weeks 2 and 4, and intraventricular hemodynamics on week 4. On day 31, the animals were euthanized for histological analysis. Echocardiographic, IVPG and hemodynamic findings indicated that the three treatment strategies shared effectively in the regeneration process. However, the MI-SC/DPP group had a unique synergistic ability to restore heart functions superior to the other treatment protocols. Histology showed that the MI-SC/DPP group presented the lowest (p < 0.05) degeneration score and fibrosis % compared to the other groups. Conclusively, stem cell-seeded DPP is a promising platform for the delivery of stem cells and restoration of heart functions post-MI.
2023年11月, 研究論文（学術雑誌）, 共同, 10, 11, DOI(公開)(r-map) - Evaluation of the efficacy of mitochondrial fission inhibitor (Mdivi-1) using non-alcoholic steatohepatitis (NASH) liver organoids
Elbadawy, Mohamed; Tanabe, Kiwamu; Yamamoto, Haru; Ishihara, Yusuke; Mochizuki, Maria; Abugomaa, Amira; Yamawaki, Hideyuki; Kaneda, Masahiro; Usui, Tatsuya; Sasaki, Kazuaki
FRONTIERS IN PHARMACOLOGY
FRONTIERS MEDIA SA
Non-alcoholic steatohepatitis (NASH) is known to progress to cirrhosis and hepatocellular carcinoma in some patients. Although NASH is associated with abnormal mitochondrial function related to lipid metabolism, mechanisms for the development and effective treatments are still unclear. Therefore, new approaches to elucidate the pathophysiology are needed. In the previous study, we generated liver organoids from different stages of NASH model mice that could recapitulate the part of NASH pathology. In the present study, we investigated the relationship between mitochondrial function and NASH disease by comparing NASH liver organoids (NLO) and control liver organoids (CLO). Compared with CLO, mitochondrial and organoid morphology was abnormal in NLO, with increased expression of mitochondrial mitogen protein, DRP1, and mitochondria-derived reactive oxygen species (ROS) production. Treatment of NLO with a DPR1 inhibitor, Mdivi-1 resulted in the improvement of morphology and the decreased expression of fibrosis-related markers, Col1a1 and Acta2. In addition, treatment of NASH model mice with Mdivi-1 showed a decrease in fatty liver. Mdivi-1 treatment also prevented fibrosis and ROS production in the liver. These results indicate that NLO undergoes enhanced metabolism and abnormal mitochondrial morphology compared with CLO. It was also suggested that Mdivi-1 may be useful as a therapeutic agent to ameliorate NASH pathology.
2023年10月12日, 研究論文（学術雑誌）, 共同, 14, DOI(公開)(r-map) - Biliary excretion and pharmacokinetics of several fluoroquinolones after intravenous injection in rabbits
Shimada, Sumire; Aboubakr, Mohamed; Elbadawy, Mohamed; Usui, Tatsuya; Sasaki, Kazuaki; Shimoda, Minoru
JOURNAL OF VETERINARY MEDICAL SCIENCE
JAPAN SOC VET SCI
The aim of this study was to measure the concentrations of enrofloxacin (ERFX) and other fluoroquinolones; orbifloxacin (OBFX), marbofloxacin (MBFX), and ofloxacin (OFLX) in the plasma and bile of rabbits after a single intravenous (IV) injection. Twenty male rabbits were divided into four groups and given each drug by IV injection into the ear vein at a dose of 5.0 mg/kg BW. The concentration of ERFX, ciprofloxacin (CPFX), OBFX, MBFX and OFLX in plasma and bile were determined by HPLC. CPFX, metabolite of ERFX, was also measured by HPLC in plasma and bile of rabbits receiving ERFX. Several pharmacokinetic parameters in plasma were calculated and biliary clearance (CLbile) was calculated from extent of biliary excretion and accumulation of AUC of each drug. After IV injection, elimination half-life (t1/2 beta) was 4.13, 3.68, 6.60, 5.14 hr; volume of distribution at a steady state (Vdss) was 1.24, 0.503, 0.771, 1.02 L/kg; and total body clearance (CLtot) was 1.05, 0.418, 0.271, 0.453 L/kg/hr, respectively. The values for CLbile for ERFX, OBFX, MBFX, and OFLX were 0.0048, 0.0050, 0.0057, and 0.0094 L/kg/hr, respectively. These values represent 0.48%, 1.2%, 2.1%, and 2.3% of the total body clearance (CLtot) of each drug, respectively. The biliary clearance of CPFX was also measured and found to be 0.0199 L/kg/hr with ERFX administration. The results showed that ERFX, OBFX, MBFX, and OFLX were not excreted into the bile to a significant extent, making them safe drugs to use in rabbits.
2023年10月, 研究論文（学術雑誌）, 共同, 85, 10, 0916-7250, DOI(公開)(r-map), 1099, 1105 - Derivation of a new model of lung adenocarcinoma using canine lung cancer organoids for translational research in pulmonary medicine
Shiota (Sato), Yomogi; Elbadawy, Mohamed; Suzuki, Kazuhiko; Tsunedomi, Ryouichi; Nagano, Hiroaki; Ishihara, Yusuke; Yamamoto, Haru; Azakami, Daigo; Uchide, Tsuyoshi; Fukushima, Ryuji; Tanaka, Ryo; Yoshida, Tomohiko; Mori, Takuya; Abugomaa, Amira; Kaneda, Masahiro; Yamawaki, Hideyuki; Shinohara, Yuta; Aboubakr, Mohamed; El-Asrag, Mohamed E.; Usui, Tatsuya; Sasaki, Kazuaki
BIOMEDICINE & PHARMACOTHERAPY
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Canine primary lung cancer (cPLC) is a rare malignant tumor in dogs, and exhibits poor prognosis. Effective therapeutic drugs against cPLC have not been established yet. Also, cPLC resembles human lung cancer in histopathological characteristics and gene expression profiles and thus could be an important research model for this disease. Threedimensional organoid culture is known to recapitulate the tissue dynamics in vivo. We, therefore, tried to generate cPLC organoids (cPLCO) for analyzing the profiles of cPLC. After samples from cPLC and the corresponding normal lung tissue were collected, cPLCO were successfully generated, which recapitulated the tissue architecture of cPLC, expressed lung adenocarcinoma marker (TTF1), and exhibited tumorigenesis in vivo. The sensitivity of cPLCO to anticancer drugs was different among strains. RNA-sequencing analysis showed significantly upregulated 11 genes in cPLCO compared with canine normal lung organoids (cNLO). Moreover, cPLCO were enriched with the MEKsignaling pathway compared with cNLO. The MEK inhibitor, trametinib decreased the viability of several strains of cPLCO and inhibited the growth of cPLC xenografts. Collectively, our established cPLCO model might be a useful tool for identifying novel biomarkers for cPLC and a new research model for dog and human lung cancer.
2023年09月, 研究論文（学術雑誌）, 共同, 165, 0753-3322, DOI(公開)(r-map) - Oral pharmacokinetics of sulfadiazine and sulfamonomethoxine in female Holstein milking cows
Tajima, Tsuyoshi; Saiga, Masumi; Yamamoto, Haru; Elbadawy, Mohamed; Abugomaa, Amira; Miura, Ryotaro; Usui, Tatsuya; Sasaki, Kazuaki; Shimoda, Minoru
JOURNAL OF VETERINARY MEDICAL SCIENCE
JAPAN SOC VET SCI
The efficacy of orally administered drugs in cattle is thought to be slow because of the anatomical and physiological features of their forestomach. Thus, parenteral routes are mainly preferred to administer drugs. However, the effect of some drugs with unique physicochemical properties was promptly obtained even after oral administration in clinically ill cattle. Therefore, the present study aimed to investigate pharmacokinetically the usefulness of the oral route in cattle by comparing the oral pharmacokinetic properties of two sulfonamides with different physicochemical properties. Sulfadiazine (SDZ) and sulfamonomethoxine (SMM) were administered by intravenous and oral route to four female Holstein cows with a 4-weeks washout period. Blood samples were collected over time, and SDZ and SMM concentrations in plasma were analyzed by HPLC. Data obtained from the same animal after intravenous and oral administration were simultaneously analyzed with the one compartment model, and kinetic parameters were calculated. The Tmax (mean & PLUSMN; SD) of SMM (2.75 & PLUSMN; 0.96 hr) was significantly achieved earlier than that of SDZ (5.00 & PLUSMN; 1.15 hr). Further, the mean absorption time of SMM (5.24 & PLUSMN; 0.69 hr) was significantly shorter than that of SDZ (5.92 & PLUSMN; 1.11 hr). Also, the half-life of absorption of SMM (3.91 & PLUSMN; 0.51 hr) was significantly shorter than that of SDZ (4.51 & PLUSMN; 0.82 hr). These data suggest that the absorption rates of highly unionized drugs (such as SMM) from the forestomach of cattle may be markedly higher than less unionized ones (such as SDZ).
2023年07月, 研究論文（学術雑誌）, 共同, 85, 7, 0916-7250, DOI(公開)(r-map), 715, 720 - Comparison of Bovine- and Porcine-Derived Decellularized Biomaterials: Promising Platforms for Tissue Engineering Applications
El-Husseiny, Hussein M.; Mady, Eman A.; Kaneda, Masahiro; Shimada, Kazumi; Nakazawa, Yasumoto; Usui, Tatsuya; Elbadawy, Mohamed; Ishihara, Yusuke; Hirose, Moeko; Kamei, Yohei; Doghish, Ahmed S.; El-Mahdy, Hesham A.; El-Dakroury, Walaa A.; Tanaka, Ryou
PHARMACEUTICS
MDPI
Animal-derived xenogeneic biomaterials utilized in different surgeries are promising for various applications in tissue engineering. However, tissue decellularization is necessary to attain a bioactive extracellular matrix (ECM) that can be safely transplanted. The main objective of the present study is to assess the structural integrity, biocompatibility, and potential use of various acellular biomaterials for tissue engineering applications. Hence, a bovine pericardium (BP), porcine pericardium (PP), and porcine tunica vaginalis (PTV) were decellularized using a Trypsin, Triton X (TX), and sodium dodecyl sulfate (SDS) (Trypsin + TX + SDS) protocol. The results reveal effective elimination of the cellular antigens with preservation of the ECM integrity confirmed via staining and electron microscopy. The elasticity of the decellularized PP (DPP) was markedly (p < 0.0001) increased. The tensile strength of DBP, and DPP was not affected after decellularization. All decellularized tissues were biocompatible with persistent growth of the adipose stem cells over 30 days. The staining confirmed cell adherence either to the peripheries of the materials or within their matrices. Moreover, the in vivo investigation confirmed the biocompatibility and degradability of the decellularized scaffolds. Conclusively, Trypsin + TX + SDS is a successful new protocol for tissue decellularization. Moreover, decellularized pericardia and tunica vaginalis are promising scaffolds for the engineering of different tissues with higher potential for the use of DPP in cardiovascular applications and DBP and DPTV in the reconstruction of higher-stress-bearing abdominal walls.
2023年07月, 研究論文（学術雑誌）, 共同, 15, 7, DOI(公開)(r-map) - Establishment of an experimental model of canine malignant mesothelioma organoid culture using a three-dimensional culture method
Sato, Yomogi; Elbadawy, Mohamed; Suzuki, Kazuhiko; Tsunedomi, Ryouichi; Nagano, Hiroaki; Ishihara, Yusuke; Yamamoto, Haru; Azakami, Daigo; Uchide, Tsuyoshi; Nabeta, Rina; Fukushima, Ryuji; Abugomaa, Amira; Kaneda, Masahiro; Yamawaki, Hideyuki; Shinohara, Yuta; Usui, Tatsuya; Sasaki, Kazuaki
BIOMEDICINE & PHARMACOTHERAPY
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Canine malignant mesothelioma (cMM) is a rare and drug-resistant malignant tumor. Due to few patients and experimental models, there have not been enough studies to demonstrate the pathogenesis of the disease and novel effective treatment for cMM. Since cMM resembles human MM (hMM) in histopathological characteristics, it is also considered a promising research model of hMM. Compared with conventional 2-dimensional (2D) culture methods, 3-dimensional (3D) organoid culture can recapitulate the properties of original tumor tissues. However, cMM organoids have never been developed. In the present study, we for the first time generated cMM organoids using the pleural effusion samples. Organoids from individual MM dogs were successfully generated. They exhibited the characteristics of MM and expressed mesothelial cell markers, such as WT-1 and mesothelin. The sensitivity to anti-cancer drugs was different in each strain of cMM organoids. RNA sequencing analysis showed cell adhesion molecule pathways were specifically upregulated in cMM organoids compared with their corresponding 2D cultured cells. Among these genes, the expression level of E-cadherin was drastically higher in the organoids than that in the 2D cells. In conclusion, our established cMM organoids might become a new experimental tool to provide new insights into canine and human MM therapy.
2023年06月, 研究論文（学術雑誌）, 共同, 162, 0753-3322, DOI(公開)(r-map) - Anti-tumor effect of trametinib in canine primary lung cancer organoids as a novel therapeutic agent
Sato, Y.; Elbadawy, M.; Yamamoto, H.; Usui, T.; Sasaki, K.
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
WILEY
2023年06月, 研究論文（国際会議プロシーディングス）, 共同, 46, 0140-7783, DOI(公開)(r-map), 40, 40 - Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against patient-derived bladder cancer organoids
Elbadawy, M.; Abugomaa, A.; Usui, T.; Sasaki, K.
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
WILEY
2023年06月, 研究論文（国際会議プロシーディングス）, 共同, 46, 0140-7783, DOI(公開)(r-map), 53, 53 - Exploring new therapeutic targets of feline mammary tumor using organoids technology
Yamamoto, H.; Elbadawy, M.; Usui, T.; Sasaki, K.
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
WILEY
2023年06月, 研究論文（国際会議プロシーディングス）, 共同, 46, 0140-7783, DOI(公開)(r-map), 71, 71 - Pharmacokinetic evaluation of oral itraconazole administration in captive King Penguins (Aptenodytes patagonicus) after single doses
Inoue, A.; Enomoto, M.; Iida, N.; Usui, T.; Sasaki, K.
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
WILEY
2023年06月, 研究論文（国際会議プロシーディングス）, 共同, 46, 0140-7783, DOI(公開)(r-map), 89, 90 - Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
Abugomaa, Amira; Elbadawy, Mohamed; Ishihara, Yusuke; Yamamoto, Haru; Kaneda, Masahiro; Yamawaki, Hideyuki; Shinohara, Yuta; Usui, Tatsuya; Sasaki, Kazuaki
FRONTIERS IN PHARMACOLOGY
FRONTIERS MEDIA SA
Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoting and anti-cancer potentials. Organoid culture can recapitulate tumor heterogeneity, epithelial environment, and genetic and molecular imprints of the original tissues. In the previous study, we generated dog bladder cancer organoids (DBCO) as a novel experimental model of muscle-invasive BCO. Therefore, the present study aimed to examine the anti-tumor potentials of Chaga mushroom extract (Chaga) against DBCO. Four strains of DBCO were used in the present study. Treatment with Chaga inhibited the cell viability of DBCO in a concentration-dependent way. Treatment of DBCO with Chaga has significantly arrested its cell cycle and induced apoptosis. Expression of bladder CSC markers, CD44, C-MYC, SOX2, and YAP1, declined in the Chaga-treated DBCO. Also, Chaga inhibited the phosphorylation of ERK in DBCO. Expression of downstream signals of ERK, C-MYC, and Cyclins (Cyclin-A2, Cyclin-D1, Cyclin-E1, and CDK4) was also inhibited by Chaga in DBCO. Interestingly, the combinational treatment of DBCO with Chaga and anti-cancer drugs, vinblastine, mitoxantrone, or carboplatin, showed a potentiating activity. In vivo, Chaga administration decreased tumor growth and weight of DBCO-derived xenograft in mice with the induction of necrotic lesions. In conclusion, Chaga diminished the cell viability of DBCO by inhibiting proliferation-related signals and stemness conditions as well as by arresting the cell cycle. Collectively, these data suggest the value of Chaga as a promising natural supplement that could potentiate the effect of adjuvant chemotherapy, lower its adverse effects, and thus, limit the recurrence and metastasis of BC.
2023年04月19日, 研究論文（学術雑誌）, 共同, 14, DOI(公開)(r-map) - Establishment of a direct 2.5D organoid culture model using companion animal cancer tissues
Abugomaa, Amira; Elbadawy, Mohamed; Yamamoto, Haru; Ayame, Hiromi; Ishihara, Yusuke; Sato, Yomogi; Yamawaki, Hideyuki; Kaneda, Masahiro; Usui, Tatsuya; Sasaki, Kazuaki
BIOMEDICINE & PHARMACOTHERAPY
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Like humans, cancer affects companion animals with similar genetic risks and incident rates. To improve treatment strategies for pet cancers, new research models are necessary. Patient-derived 3D organoid culture models are valuable and ensure the development of new effective therapies. In the previous study, we established a 3D organoid-derived 2.5D organoid culture model that recapitulated some characteristics of their parental 3D organoids. In the present study, we aimed to generate a 2.5D organoid culture model directly from cancer -diseased dogs and cats using special 2.5D media. The primary cultured cells in 2.5D media (direct 2.5D orga-noids) showed better attachment, growth, marker expression, and faster proliferation speed than those cultured in normal Dulbecco's Modified Eagle Medium media. The direct 2.5D organoids showed expression of each specific marker to their original cancer tissues and exhibited tumorigenesis in vivo. Moreover, the direct 2.5D organoids exhibited concentration-dependent responses to anti-cancer drugs, and different sensitivity profiles were shown among the strains. Our data suggest that the direct 2.5D organoid culture model might become a useful tool beyond 2D cell lines to study cancer biology in companion animals and could provide new platforms for screening the anti-cancer drugs.
2022年10月, 研究論文（学術雑誌）, 共同, 154, 0753-3322, DOI(公開)(r-map) - Establishment of an experimental model of normal dog bladder organoid using a three-dimensional culture method
Elbadawy, Mohamed; Fujisaka, Kodai; Yamamoto, Haru; Tsunedomi, Ryouichi; Nagano, Hiroaki; Ayame, Hiromi; Ishihara, Yusuke; Mori, Takashi; Azakami, Daigo; Uchide, Tsuyoshi; Fukushima, Ryuji; Abugomaa, Amira; Kaneda, Masahiro; Yamawaki, Hideyuki; Shinohara, Yuta; Omatsu, Tsutomu; Mizutani, Tetsuya; Usui, Tatsuya; Sasaki, Kazuaki
BIOMEDICINE & PHARMACOTHERAPY
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Dog bladder cancer (BC) is mostly muscle-invasive (MI) with poor prognosis, and its pathogenesis is close to human MIBC. Three-dimensional (3D) organoid culture ensures novel knowledge on cancer diseases including BC. Recently, we have established dog BC organoids (BCO) using their urine samples. BCO recapitulated the epithelial structures, characteristics, and drug sensitivity of BC-diseased dogs. However, organoids from dog normal bladder epithelium are not established yet. Therefore, the present study aimed to establish dog normal bladder organoids (NBO) for further understanding the pathogenesis of dog BC and human MIBC. The established NBO underwent various analyzes including cell marker expressions, histopathological structures, cancer-related gene expression patterns, and drug sensitivity. NBO could be produced non-invasively with a continuous culturing and recapitulated the structures and characteristics of the dog's normal bladder mucosal tissues. Different drug sensitivities were observed in each NBO. The analysis of RNA sequencing revealed that several novel genes were changed in NBO compared with BCO. NBO showed a higher expression of p53 and E-cadherin, but a lower expression of MDM2 and Twist1 compared with BCO. These results suggest that NBO could be a promising experimental 3D model for studying the developmental mechanisms of dog BC and human MIBC.
2022年07月, 研究論文（学術雑誌）, 共同, 151, 0753-3322, DOI(公開)(r-map) - Effect of the liquid form of traditional Chinese medicine, Hozen-S, on gastric motility in dogs
Shinohara, Yuta; Elbadawy, Mohamed; Yamanaka, Megumi; Yamamoto, Haru; Abugomaa, Amira; Usui, Tatsuya; Sasaki, Kazuaki
JOURNAL OF VETERINARY MEDICAL SCIENCE
JAPAN SOC VET SCI
Juzen-taiho-to, a traditional Chinese herbal medicine, is used for patients with anorexia and fatigue in human medicine. In our previous study, granulated Juzen-taiho-to improved vincristine-induced gastrointestinal adverse effects through increasing gastric motility in dogs. As the effect of Hozen-S, the sweet liquid form of Juzen-taiho-to, on dog gastric motility has not been investigated, we examined the effect of administration of Hozen-S on gastric motility. Furthermore, we assessed dog plasma ghrelin level to further elucidate the mechanism of the effect of Hozen-S on gastric contraction. Finally, we assessed the palatability of Hozen-S compared to granulated Juzen-taiho-to and its effect on body weight in dogs. Administration of Hozen-S significantly increased gastric motility, plasma ghrelin concentration, and body weight. A palatability evaluation revealed that the dogs preferred Hozen-S to granulated Juzen-taiho-to. In conclusion, Hozen-S administration to dogs promoted gastric motility by raising plasma ghrelin levels. Considering these functional and palatability data, Hozen-S may replace granulated type Juzen-taiho-to and become a prominent traditional Chinese veterinary medicament.
2022年06月, 研究論文（学術雑誌）, 共同, 84, 6, 0916-7250, DOI(公開)(r-map), 841, 846 - Anti-malarial activity in a Chinese herbal supplement containing Inonotus obliquus and Panax notoginseng
Endo, Takuro; Nakagomi, Yuki; Kawaguchi, Eri; Hayakawa, Eri Saki H.; Vu, Hoai Nam; Takemae, Hitoshi; Shinohara, Yuta; Yang, Da; Usui, Tatsuya; Mizutani, Tetsuya; Nakao, Yoichi; Furuya, Tetsuya
PARASITOLOGY INTERNATIONAL
ELSEVIER IRELAND LTD
Plasmodium falciparum, the most virulent human malaria parasite, causes serious diseases among the infected patients in the world and is particularly important in African regions. Although artemisinin combination therapy is recommended by the WHO for treatment of P. falciparum-malaria, the emergence of artemisinin-resistant parasites has become a serious issue which underscores the importance of sustained efforts to obtain novel chemotherapeutic agents against malaria. As a part of such efforts, thirty-nine herbal extracts from traditional Chinese medicine (TCM) were assayed for their anti-malarial activity using 3D7 strain of P. falciparum. Three herbal supplements appeared to possess higher specific anti-malarial activity than the others. One of them (D3) was separated by two sequential fractionations with reverse-phase (the first step) and normal-phase (the second step) liquid chromatography, in which some fractions resulted in higher specific activities than those of D3 or the previous fractions. Cell toxicity assay was performed with the fractions of the first fractionation and demonstrated no obvious cell toxicity. These results suggest that structure determination of the major compound for the anti-malarial activity in D3 may help the development of more potent chemicals in the future.
2022年04月, 研究論文（学術雑誌）, 共同, 87, 1383-5769, DOI(公開)(r-map) - The potential of organoids in toxicologic pathology: role of toxicologic pathologists in in vitro chemical hepatotoxicity assessment
Yoshida, Toshinori; Kobayashi, Mio; Uomoto, Suzuka; Ohshima, Kanami; Hara, Emika; Katoh, Yoshitaka; Takahashi, Naofumi; Harada, Takanori; Usui, Tatsuya; Elbadawy, Mohamed; Shibutani, Makoto
JOURNAL OF TOXICOLOGIC PATHOLOGY
JAPANESE SOC TOXICOLOGIC PATHOLOGY
The development of in vitro toxicity assessment methods using cultured cells has gained popularity for promoting animal welfare in animal experiments. Herein, we briefly discuss the current status of hepatoxicity assessment using human-and rat-derived hepatocytes; we focus on the liver organoid method, which has been extensively studied in recent years, and discuss how toxicologic pathologists can use their knowledge and experience to contribute to the development of in vitro chemical hepatotoxicity assessment methods for drugs, pesticides, and chemicals. We also propose how toxicological pathologists should assess toxicity regarding the putative distribution of undifferentiated and differentiated cells in the organoid when liver organoids are observed in hematoxylin and eosin-stained specimens. This was done while considering the usefulness and limitations of in vitro studies for toxicologic pathology assessment.
2022年, 研究論文（学術雑誌）, 共同, 35, 3, 0914-9198, DOI(公開)(r-map), 225, 235 - Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
Salahudeen, Ameen A.; Choi, Shannon S.; Rustagi, Arjun; Zhu, Junjie; van Unen, Vincent; De la O, Sean M.; Flynn, Ryan A.; Margalef-Catala, Mar; Santos, Antonio J. M.; Ju, Jihang; Batish, Arpit; Usui, Tatsuya; Zheng, Grace X. Y.; Edwards, Caitlin E.; Wagar, Lisa E.; Luca, Vincent; Anchang, Benedict; Nagendran, Monica; Nguyen, Khanh; Hart, Daniel J.; Terry, Jessica M.; Belgrader, Phillip; Ziraldo, Solongo B.; Mikkelsen, Tarjei S.; Harbury, Pehr B.; Glenn, Jeffrey S.; Garcia, K. Christopher; Davis, Mark M.; Baric, Ralph S.; Sabatti, Chiara; Amieva, Manuel R.; Blish, Catherine A.; Desai, Tushar J.; Kuo, Calvin J.
NATURE
NATURE RESEARCH
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate the investigation of pathologies such as interstitial lung disease, cancer and coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we describe the development of a long-term feeder-free, chemically defined culture system for distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5(+) basal cells. AT2 organoids were able to differentiate into AT1 cells, and basal cell organoids developed lumens lined with differentiated club and ciliated cells. Single-cell analysis of KRT5(+) cells in basal organoids revealed a distinct population of ITGA6(+)ITGB4(+) mitotic cells, whose offspring further segregated into a TNFRSF12A(hi) subfraction that comprised about ten per cent of KRT5(+) basal cells. This subpopulation formed clusters within terminal bronchioles and exhibited enriched clonogenic organoid growth activity. We created distal lung organoids with apical-out polarity to present ACE2 on the exposed external surface, facilitating infection of AT2 and basal cultures with SARS-CoV-2 and identifying club cells as a target population. This long-term, feeder-free culture of human distal lung organoids, coupled with single-cell analysis, identifies functional heterogeneity among basal cells and establishes a facile in vitro organoid model of human distal lung infections, including COVID-19-associated pneumonia. A long-term culture method for organoids derived from single adult human lung cells is used to identify progenitor cells and study SARS-CoV-2 infection.
2020年12月24日, 研究論文（学術雑誌）, 共同, 588, 7839, 0028-0836, DOI(公開)(r-map), 670, + - Autophagy regulates levels of tumor suppressor enzyme protein phosphatase 6
Fujiwara, Nobuyuki; Shibutani, Shusaku; Sakai, Yusuke; Watanabe, Toshio; Kitabayashi, Issay; Oshima, Hiroko; Oshima, Masanobu; Hoshida, Hisashi; Akada, Rinji; Usui, Tatsuya; Ohama, Takashi; Sato, Koichi
CANCER SCIENCE
WILEY
Protein phosphatase 6 (PP6) is an essential serine/threonine protein phosphatase that acts as an important tumor suppressor. However, increased protein levels of PP6 have been observed in some cancer types, and they correlate with poor prognosis in glioblastoma. This raises a question about how PP6 protein levels are regulated in normal and transformed cells. In this study, we show that PP6 protein levels increase in response to pharmacologic and genetic inhibition of autophagy. PP6 associates with autophagic adaptor protein p62/SQSTM1 and is degraded in a p62-dependent manner. Accordingly, protein levels of PP6 and p62 fluctuate in concert under different physiological and pathophysiological conditions. Our data reveal that PP6 is regulated by p62-dependent autophagy and suggest that accumulation of PP6 protein in tumor tissues is caused at least partially by deficiency in autophagy.
2020年12月, 研究論文（学術雑誌）, 共同, 111, 12, 1347-9032, DOI(公開)(r-map), 4371, 4380 - Establishment of 2.5D organoid culture model using 3D bladder cancer organoid culture
Abugomaa, Amira; Elbadawy, Mohamed; Yamanaka, Megumi; Goto, Yuta; Hayashi, Kimika; Mori, Takashi; Uchide, Tsuyoshi; Azakami, Daigo; Fukushima, Ryuji; Yoshida, Toshinori; Shibutani, Makoto; Yamashita, Risako; Kobayashi, Mio; Yamawaki, Hideyuki; Shinohara, Yuta; Kaneda, Masahiro; Usui, Tatsuya; Sasaki, Kazuaki
SCIENTIFIC REPORTS
NATURE PUBLISHING GROUP
Three-dimensional (3D) organoid culture holds great promises in cancer precision medicine. However, Matrigel and stem cell-stimulating supplements are necessary for culturing 3D organoid cells. It costs a lot of money and consumes more time and effort compared with 2D cultured cells. Therefore, the establishment of cheaper and Matrigel-free organoid culture that can maintain the characteristics of a part of 3D organoids is demanded. In the previous study, we established a dog bladder cancer (BC) 3D organoid culture system by using their urine samples. Here, we successfully isolated cells named 2.5D organoid from multiple strains of dog BC 3D organoids using 2.5 organoid media. The cell proliferation speed of 2.5D organoids was faster than parental 3D organoid cells. The expression pattern of stem cell markers was close to 3D organoids. Injection of 2.5D organoid cells into immunodeficient mice formed tumors and showed the histopathological characteristics of urothelial carcinoma similar to the injection of dog BC 3D organoids. The 2.5D organoids had a similar sensitivity profile for anti-cancer drug treatment to their parental 3D organoids. These data suggest that our established 2.5D organoid culture method might become a reasonable and useful tool instead of 3D organoids in dog BC research and therapy.
2020年06月10日, 研究論文（学術雑誌）, 共同, 10, 1, 2045-2322, DOI(公開)(r-map) - Development of Prostate Cancer Organoid Culture Models in Basic Medicine and Translational Research
Elbadawy, Mohamed; Abugomaa, Amira; Yamawaki, Hideyuki; Usui, Tatsuya; Sasaki, Kazuaki
CANCERS
MDPI
Prostate cancer (PC) is the most prevalent cancer in men and the second main cause of cancer-related death in Western society. The lack of proper PC models that recapitulate the molecular and genomic landscape of clinical disease has hampered progress toward translational research to understand the disease initiation, progression, and therapeutic responses in each patient. Although several models have been developed, they hardly emulated the complicated PC microenvironment. Precision medicine is an emerging approach predicting appropriate therapies for individual cancer patients by means of various analyses of individual genomic profiling and targeting specific cancer pathways. In PC, precision medicine also has the potential to impose changes in clinical practices. Here, we describe the various PC models with special focus on PC organoids and their values in basic medicine, personalized therapy, and translational researches in vitro and in vivo, which could help to achieve the full transformative power of cancer precision medicine.
2020年04月, 研究論文（学術雑誌）, 共同, 12, 4, DOI(公開)(r-map) - Efficacy of primary liver organoid culture from different stages of non-alcoholic steatohepatitis (NASH) mouse model
Elbadawy, Mohamed; Yamanaka, Megumi; Goto, Yuta; Hayashi, Kimika; Tsunedomi, Ryouichi; Hazama, Shoichi; Nagano, Hiroaki; Yoshida, Toshinori; Shibutani, Makoto; Ichikawa, Ryo; Nakahara, Junta; Omatsu, Tsutomu; Mizutani, Tetsuya; Katayama, Yukie; Shinohara, Yuta; Abugomaa, Amira; Kaneda, Masahiro; Yamawaki, Hideyuki; Usui, Tatsuya; Sasaki, Kazuaki
BIOMATERIALS
ELSEVIER SCI LTD
Non-alcoholic steatohepatitis (NASH) is associated with liver fibrosis and cirrhosis, which eventually leads to hepatocellular carcinoma. Although several animal models were developed to understand the mechanisms of NASH pathogenesis and progression, it remains obscure. A 3D organoid culture system can recapitulate organ structures and maintain gene expression profiles of original tissues. We therefore tried to generate liver organoids from different degrees [defined as mild (NASH A), moderate (NASH B) and severe (NASH C)] of methionine- and choline-deficient diet-induced NASH model mice and analyzed the difference of their architecture, cell components, organoid-forming efficacy, and gene expression profiles. Organoids from each stage of NASH model mice were successfully generated. Interestingly, epithelial-mesenchymal transition was observed in NASH C organoids. Expression of Collagen I and an activated hepatic stellite cell marker, alpha-sma was upregulated in the liver organoids from NASH B and C mice. The analysis of RNA sequencing revealed that several novel genes were upregulated in all NASH liver organoids. These results suggest that our generated liver organoids from different stages of NASH diseased mice might become a useful tool for in vitro studies of the molecular mechanism of NASH development and also for identifying novel biomarkers for early diagnosis of NASH disease.
2020年04月, 研究論文（学術雑誌）, 共同, 237, 0142-9612, DOI(公開)(r-map) - Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer
Abugomaa, Amira; Elbadawy, Mohamed; Yamawaki, Hideyuki; Usui, Tatsuya; Sasaki, Kazuaki
CELLS
MDPI
Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized therapy and regular follow-up are the keys to a successful outcome. Cancer stem cells (CSCs) are the leading power behind tumor growth, with the ability of self-renewal, metastasis, and resistance to conventional chemotherapy. The fast-developing CSC field with robust genome-wide screening methods has found a platform for establishing more reliable therapies to target tumor-initiating cell populations. However, the high heterogeneity of the CSCs in BC disease remains a large issue. Therefore, in the present review, we discuss the various types of bladder CSC heterogeneity, important regulatory pathways, roles in tumor progression and tumorigenesis, and the experimental culture models. Finally, we describe the current stem cell-based therapies for BC disease.
2020年01月, 研究論文（学術雑誌）, 共同, 9, 1, DOI(公開)(r-map) - Efficacy of Juzen-taiho-to against vincristine-induced toxicity in dogs
Shinohara, Yuta; Nishino, Yoko; Yamanaka, Megumi; Ohmori, Keitaro; Elbadawy, Mohamed; Usui, Tatsuya; Sasaki, Kazuaki
JOURNAL OF VETERINARY MEDICAL SCIENCE
JAPAN SOC VET SCI
Vincristine, one of the anti-cancer drugs used in veterinary practice, has adverse hematological and gastrointestinal effects in dogs. Juzen-taiho-to is a traditional Chinese medicine used for patients with anorexia in human medicine. However, the protective effects of Juzen-taiho-to against anti-cancer drug-induced toxicity in dogs have not been investigated. We therefore examined whether the administration of Juzen-taiho-to to dogs affects gastric motility, and vincristine-induced gastrointestinal and hematological toxicity. The study was composed of three trials. In the first trial, Juzen-taiho-to (450 mg/kg/day) was orally administered to five dogs. In the second and third trials, vincristine (0.75 mg/m(2)) was intravenously administered to each dog in the absence or presence of Juzen-taiho-to (450 mg/kg/day). During these trials, gastric motility and blood parameters were assessed. Juzen-taiho-to increased gastric motility and improved vincristine-induced gastrointestinal, but not hematological, adverse effects in dogs. This study suggested that Juzen-taiho-to may be applicable for gastrointestinal care in dogs receiving chemotherapy.
2019年12月, 研究論文（学術雑誌）, 共同, 81, 12, 0916-7250, DOI(公開)(r-map), 1810, 1816 - Possible anti-oxidative effects of long-term administration of Juzen-taiho-to in dogs
Shinohara, Yuta; Oyama, Ayaka; Usui, Tatsuya; Sasaki, Kazuaki
JOURNAL OF VETERINARY MEDICAL SCIENCE
JAPAN SOC VET SCI
It is known that oxidative stress is related to disease in humans and dogs. Many traditional Chinese medicines have been reported to have anti-oxidative effects, but there are no reports that they have anti-oxidative effects in dogs. In this study, we examined the anti-oxidative effects of Juzen-taiho-to, a traditional Chinese medicine, in dogs. Five healthy female beagle dogs (38-41 months of age weighing 8.6-10.7 kg) were orally administered Juzen-taiho-to at 450 mg/kg with food for 28 days. Blood samples were taken from all five dogs on days 0, 7, 14, 21, and 28. Using the blood samples, improvement of the antioxidant level as assessed by the biological antioxidant potential (BAP), reduced oxidative stress level as assessed by derivatives of reactive oxygen metabolites (d-ROMs), and improvement of blood fluidity were examined. Regarding the antioxidant level and blood fluidity, no significant difference was observed, but the oxidative stress level on days 14, 21, and 28 was significantly lower than that on day 0. Thus, Juzen-taiho-to may have anti-oxidative effects in dogs by reducing oxidative stress and be useful for oxidative stress-related diseases in dogs.
2019年11月, 研究論文（学術雑誌）, 共同, 81, 11, 0916-7250, DOI(公開)(r-map), 1616, 1620 - Establishment of a novel experimental model for muscle-invasive bladder cancer using a dog bladder cancer organoid culture
Elbadawy, Mohamed; Usui, Tatsuya; Mori, Takashi; Tsunedomi, Ryouichi; Hazama, Shoichi; Nabeta, Rina; Uchide, Tsuyoshi; Fukushima, Ryuji; Yoshida, Toshinori; Shibutani, Makoto; Tanaka, Takaharu; Masuda, Sosuke; Okada, Rena; Ichikawa, Ryo; Omatsu, Tsutomu; Mizutani, Tetsuya; Katayama, Yukie; Noguchi, Shunsuke; Iwai, Satomi; Nakagawa, Takayuki; Shinohara, Yuta; Kaneda, Masahiro; Yamawaki, Hideyuki; Sasaki, Kazuaki
CANCER SCIENCE
WILEY
In human and dogs, bladder cancer (BC) is the most common neoplasm affecting the urinary tract. Dog BC resembles human muscle-invasive BC in histopathological characteristics and gene expression profiles, and could be an important research model for this disease. Cancer patient-derived organoid culture can recapitulate organ structures and maintains the gene expression profiles of original tumor tissues. In a previous study, we generated dog prostate cancer organoids using urine samples, however dog BC organoids had never been produced. Therefore we aimed to generate dog BC organoids using urine samples and check their histopathological characteristics, drug sensitivity, and gene expression profiles. Organoids from individual BC dogs were successfully generated, expressed urothelial cell markers (CK7, CK20, and UPK3A) and exhibited tumorigenesis in vivo. In a cell viability assay, the response to combined treatment with a range of anticancer drugs (cisplatin, vinblastine, gemcitabine or piroxicam) was markedly different in each BC organoid. In RNA-sequencing analysis, expression levels of basal cell markers (CK5 and DSG3) and several novel genes (MMP28, CTSE, CNN3, TFPI2, COL17A1, and AGPAT4) were upregulated in BC organoids compared with normal bladder tissues or two-dimensional (2D) BC cell lines. These established dog BC organoids might be a useful tool, not only to determine suitable chemotherapy for BC diseased dogs but also to identify novel biomarkers in human muscle-invasive BC. In the present study, for the 1st time, dog BC organoids were generated and several specifically upregulated organoid genes were identified. Our data suggest that dog BC organoids might become a new tool to provide fresh insights into both dog BC therapy and diagnostic biomarkers.
2019年09月02日, 研究論文（学術雑誌）, 共同, 110, 9, 1347-9032, DOI(公開)(r-map), 2806, 2821 - Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer
Elbadawy, Mohamed; Usui, Tatsuya; Yamawaki, Hideyuki; Sasaki, Kazuaki
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
MDPI
Myc is a nuclear transcription factor that mainly regulates cell growth, cell cycle, metabolism, and survival. Myc family proteins contain c-Myc, n-Myc, and l-Myc. Among them, c-Myc can become a promising therapeutic target molecule in cancer. Cancer stem cells (CSCs) are known to be responsible for the therapeutic resistance. In the previous study, we demonstrated that c-Myc mediates drug resistance of colorectal CSCs using a patient-derived primary three-dimensional (3D) organoid culture. In this review, we mainly focus on the roles of c-Myc-related signaling in the regulation of CSCs, chemotherapy resistance, and colorectal cancer organoids. Finally, we introduce the various types of c-Myc inhibitors and propose the possibility of c-Myc as a therapeutic target against colorectal cancer.
2019年05月01日, 研究論文（学術雑誌）, 共同, 20, 9, DOI(公開)(r-map) - Pericardial Mesothelioma in a Dog: The Feasibility of Ultrasonography in Monitoring Tumor Progression
Nabeta, Rina; Nakagawa, Yuki; Chiba, Shiori; Hou Xiantao; Usui, Tatsuya; Suzuki, Kazuhiko; Furuya, Tetsuya; Fukushima, Ryuji; Uchide, Tsuyoshi
FRONTIERS IN VETERINARY SCIENCE
FRONTIERS MEDIA SA
A 6-year-old neutered male Yorkshire Terrier presented with recurrent pericardial effusion. Although clinical examinations including computed tomography were inconclusive, an exploratory thoracotomy revealed multiple small nodules and plaques on the inner surface of the pericardial sac (Day 1). A subtotal pericardiectomy was performed to prevent cardiac tamponade due to the increasing pericardial effusion, and the resected section of the pericardium was histopathologically diagnosed with mesothelioma. After surgery, chemotherapy with intrathoracic carboplatin was commenced. During the course of the treatment, a detailed follow-up ultrasonographic scan was performed to detect early lesions disseminated on the pleura, originating from the primary pericardial mesothelioma. On Day 101, the minute pleural nodules, which were disseminated lesions as predicted, were successfully imaged by ultrasonography. As the clinical stage advanced, the nodules were observed to gradually increase in size and number, implying tumor progression. These observations highlight the feasibility of ultrasonography in detecting minute disseminated lesions at an early stage, monitoring tumor progression, and thereby, predicting the prognosis of canine pericardial mesothelioma.
2019年04月18日, 研究論文（学術雑誌）, 共同, 6, 2297-1769, DOI(公開)(r-map), 121 - Novel Functions of Death-Associated Protein Kinases through Mitogen-Activated Protein Kinase-Related Signals.
Elbadawy M, Usui T, Yamawaki H, Sasaki K.
Int J Mol Sci.
2018年10月04日, 研究論文（学術雑誌）, 共同, 19, 10, DOI(公開)(r-map), E3031 - A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation
Yabe R, Tsuji S, Mochida S, Ikehara T, Usui T, Ohama T, Sato K
FEBS Open Bio.
2018年08月01日, 8, 9, DOI(公開)(r-map), 1486, 1496 - Development of an Experimental Model for Analyzing Drug Resistance in Colorectal Cancer
Elbadawy, Mohamed; Usui, Tatsuya; Yamawaki, Hideyuki; Sasaki, Kazuaki
CANCERS
MDPI
Colorectal cancer (CRC) is one of the most common cancers, for which combination treatment of chemotherapy is employed. However, most patients develop drug resistance during the course of treatment. To clarify the mechanisms of drug resistance, various research models have been developed. Recently, we established a human CRC patients-derived three-dimensional (3D) culture system using an air-liquid interface organoid method. It contained numerous cancer stem cells and showed resistance to 5-fluorouracil and Irinotecan. In this review, we introduce conventional and our established models for studying drug resistance in CRC.
2018年06月, 研究論文（学術雑誌）, 共同, 10, 6, 2072-6694, DOI(公開)(r-map) - Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture
Usui, Tatsuya; Sakurai, Masashi; Umata, Koji; Elbadawy, Mohamed; Ohama, Takashi; Yamawaki, Hideyuki; Hazama, Shoichi; Takenouchi, Hiroko; Nakajima, Masao; Tsunedomi, Ryouichi; Suzuki, Nobuaki; Nagano, Hiroaki; Sato, Koichi; Kaneda, Masahiro; Sasaki, Kazuaki
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
MDPI
Colorectal cancer is one of the most common causes of cancer death worldwide. In patients with metastatic colorectal cancer, combination treatment with several anti-cancer drugs is employed and improves overall survival in some patients. Nevertheless, most patients with metastatic disease are not cured owing to the drug resistance. Cancer stem cells are known to regulate resistance to chemotherapy. In the previous study, we established a novel three-dimensional organoid culture model from tumor colorectal tissues of human patients using an air-liquid interface (ALI) method, which contained numerous cancer stem cells and showed resistance to 5-fluorouracil (5-FU) and Irinotecan. Here, we investigate which inhibitor for stem cell-related signal improves the sensitivity for anti-cancer drug treatment in tumor ALI organoids. Treatment with Hedgehog signal inhibitors (AY9944, GANT61) decreases the cell viability of organoids compared with Notch (YO-01027, DAPT) and Wnt (WAV939, Wnt-C59) signal inhibitors. Combination treatment of AY9944 or GANT61 with 5-FU, Irinotecan or Oxaliplatin decreases the cell viability of tumor organoids compared with each anti-cancer drug alone treatment. Treatment with AY9944 or GANT61 inhibits expression of stem cell markers c-Myc, CD44 and Nanog, likely through the decrease of their transcription factor, GLI-1 expression. Combination treatment of AY9944 or GANT61 with 5-FU or Irinotecan also prevents colony formation of colorectal cancer cell lines HCT116 and SW480. These findings suggest that Hedgehog signals mediate anti-cancer drug resistance in colorectal tumor patient-derived ALI organoids and that the inhibitors are useful as a combinational therapeutic strategy against colorectal cancer.
2018年04月, 研究論文（学術雑誌）, 共同, 19, 4, 1422-0067, DOI(公開)(r-map) - Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis
Enjoji, Shuhei; Yabe, Ryotaro; Tsuji, Shunya; Yoshimura, Kazuhiro; Kawasaki, Hideyoshi; Sakurai, Masashi; Sakai, Yusuke; Takenouchi, Hiroko; Yoshino, Shigefumi; Hazama, Shoichi; Nagano, Hiroaki; Oshima, Hiroko; Oshima, Masanobu; Vitek, Michael P.; Matsuura, Tetsuya; Hippo, Yoshitaka; Usui, Tatsuya; Ohama, Takashi; Sato, Koichi
MOLECULAR CANCER RESEARCH
AMER ASSOC CANCER RESEARCH
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possesses the ability to self-renew and dedifferentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown. Increased kinase and decreased phosphatase activity are hallmarks of oncogenic signaling. Protein phosphatase 2A (PP2A) functions as a tumor-suppressor enzyme, and elevated levels of SET/I2PP2A, an endogenous PP2A protein inhibitor, are correlated with poor prognosis of several human cancers. Here, it was determined that SET expression was elevated in tumor tissue in a gastric cancer mouse model system, and SET expression was positively correlated with poor survival of human gastric cancer patients. Mechanistically, SET knockdown decreased E2F1 levels and suppressed the stemness of cancer cell lines. Immunoprecipitations show SET associated with the PP2A-B56 complex, and the B56 subunit interacted with the E2F1 transcription factor. Treatment of gastric cancer cells with the SET-targeting drug OP449 increased PP2A activity, decreased E2F1 protein levels, and suppressed stemness of cancer cells. These data indicate that a SET/PP2A/E2F1 axis regulates cancer cell stemness and is a potential target for gastric cancer therapy.
2018年03月, 研究論文（学術雑誌）, 共同, 16, 3, 1541-7786, DOI(公開)(r-map), 554, 563 - Preparation of human primary colon tissue-derived organoid using air liquid interface culture
Usui T, Sakurai M, Umata K, Yamawaki H, Ohama T, Sato K.
Current Protocols in Toxicology
2018年02月21日, 75, DOI(公開)(r-map), 22.6.1, 22.6.7 - Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells
Usui, Tatsuya; Sakurai, Masashi; Nishikawa, Shimpei; Umata, Koji; Nemoto, Yuki; Haraguchi, Tomoya; Itamoto, Kazuhito; Mizuno, Takuya; Noguchi, Shunsuke; Mori, Takashi; Iwai, Satomi; Nakagawa, Takayuki; Yamawaki, Hideyuki; Ohama, Takashi; Sato, Koichi
CANCER SCIENCE
WILEY
Dog spontaneously develop prostate cancer (PC) like humans. Because most dogs with PC have a poor prognosis, they could be used as a translational model for advanced PC in humans. Stem cell-derived 3-D organoid culture could recapitulate organ structures and physiology. Using patient tissues, a human PC organoid culture system was established. Recent study has shown that urine cells also possess the characteristic of stem cells. However, urine cell-derived PC organoids have never been produced. Therefore, we generated PC organoids using the dog urine samples. Urine organoids were successfully generated from each dog with PC. Each organoid showed cystic structures and resembled the epithelial structures of original tissues. Expression of an epithelial cell marker, E-cadherin, and a myofibloblast marker, -SMA, was observed in the urine organoids. The organoids also expressed a basal cell marker, CK5, and a luminal cell marker, CK8. CD49f-sorted basal cell organoids rapidly grew compared with CD24-sorted luminal cell organoids. The population of CD44-positive cells was the highest in both organoids and the original urine cells. Tumors were successfully formed with the injection of the organoids into immunodeficient mice. Treatment with a microtubule inhibitor, docetaxel, but not a cyclooxygenase inhibitor, piroxicam, and an mTOR inhibitor, rapamycin, decreased the cell viability of organoids. Treatment with a Hedgehog signal inhibitor, GANT61, increased the radiosensitivity in the organoids. These findings revealed that PC organoids using urine might become a useful tool for investigating the mechanisms of the pathogenesis and treatment of PC in dogs.
2017年12月, 研究論文（学術雑誌）, 共同, 108, 12, 1349-7006, DOI(公開)(r-map), 2383, 2392 - Establishment of a novel three-dimensional primary culture model for hippocampal neurogenesis
Usui T, Sakurai M, Kawasaki H, Ohama T, Yamawaki H, Sato K
Physiological Reports
2017年06月05日, 5, 12, DOI(公開)(r-map), e13318 - The role of SET/I2PP2A in canine mammary tumors.
Kake S, Tsuji S, Enjoji S, Hanasaki S, Hayase H, Yabe R, Tanaka Y, Nakagawa T, Liu HP, Chang SC, Usui T, Ohama T, Sato K.
Scientific Reports
2017年06月, 7, 1, DOI(公開)(r-map), 4279 - Regulation of intestinal myofibroblasts by KRas-mutated colorectal cancer cells through heparin-binding epidermal growth factor-like growth factor
Kawasaki, Hideyoshi; Saotome, Takuya; Usui, Tatsuya; Ohama, Takashi; Sato, Koichi
ONCOLOGY REPORTS
SPANDIDOS PUBL LTD
In colorectal cancer, gain-of-function mutations in KRas play a critical role in malignant transformation. Tumor growth in colorectal cancer is known to be promoted by the intestinal myofibroblasts (IMFs) that localize adjacent to the cancer cells, but the mechanisms of interaction between KRasmutated cancer cells and the myofibroblasts remain unclear. Here, we investigated the effects of KRas-mutated cells on the behavior of myofibroblasts by using mouse primary IMFs and cells of an IMF cell line (LmcMF) and a mouse colon epithelial cell line (aMoCl). Conditioned medium (CM) was collected from aMoC1 cells overexpressing a control vector or KRasV12 vector (KRasV12-CM), and the effects of KRasV12-CM on IMFs were analyzed by performing proliferation assays, wound-healing assays, Boyden chamber assays, and western blotting. Whereas KRasV12-CM exerted little effect on the differentiation and proliferation of primary IMFs, the CM promoted migration of both primary IMFs and LmcMF cells. In KRasV12-overexpressing aMoCl cells, mRNA expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) was higher than in mock-transfected aMoC1 cells, and HB-EGF promoted the migration of primary IMFs and LmcMF cells. Moreover, KRasV12-CM-induced IMF migration was suppressed by dacomitinib, an inhibitor of HB-EGF receptors. Notably, in LmcMF cells, both KRasV12-CM and HB-EGF activated extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK), whereas KRasV12CM-induced migration of IMFs was suppressed following treatment with either an ERK inhibitor (FR180204) or a JNK inhibitor (SP600125). These results suggest that HB-EGF secreted from KRas-mutated colorectal cancer cells promotes IMF migration through ERK and JNK activation, which, in turn, could support cancer progression.
2017年05月, 研究論文（学術雑誌）, 共同, 37, 5, 1021-335X, DOI(公開)(r-map), 3128, 3136 - Regulation of intestinal myofibroblasts by KRas-mutated colorectal cancer cells through heparin-binding epidermal growth factor-like growth factor.
Kawasaki H, Saotome T, Usui T, Ohama T, Sato K.
ONCOLOGY REPORTS
2017年03月, 37, 5, DOI(公開)(r-map), 3128, 3136 - Death-associated protein kinase 3 controls the tumor progression of A549 cells through ERK MAPK/c-Myc signaling
Kake, Satoru; Usui, Tatsuya; Ohama, Takashi; Yamawaki, Hideyuki; Satoi, Koichi
ONCOLOGY REPORTS
SPANDIDOS PUBL LTD
Death-associated protein kinases (DAPKs) are members of the serine/threonine protein kinase family, which regulate cell death. Although DAPK3 has been implicated as a tumor suppressor, a recent study revealed an oncogenic role of DAPK3. However, the role of DAPK3 in non-small cell lung cancer (NSCLC) remains unclear. Therefore, we examined whether DAPK3 controls the progression of NSCLC using the NSCLC cell line, A549. We generated A549 cells stably expressing small hairpin RNA (shRNA) targeting DAPK3. In the A549 cells, the protein level of DAPK3 was decreased and the cell proliferation was inhibited. DAPK3 knockdown caused WC-, cell cycle arrest as assessed by flow cytometric assay and reduced cyclin D1 expression in A549 cells. Phosphorylation of ERK and c-Myc, but not Akt and JNK, was inhibited by DAPK3 knockdown. Cell migration and invasion were also inhibited by DAPK3 knockdown as determined by a Boyden chamber assay and an invasion assay, respectively. Moreover, DAPK3 knockdown inhibited anchorage-independent cell growth as determined by soft-agar colony formation assay. In a mouse xenograft model, tumors derived from DAPK3-knockdown cells exhibited reduced tumor growth. The present results demonstrated for the first time that DAPK3 controls proliferation, migration, invasion, soft-agar colony formation and tumor growth through activation of ERK/c-Myc signaling in A549 cells. These findings indicate that DAPK3 may be a novel target for the treatment of NSCLC.
2017年02月, 研究論文（学術雑誌）, 共同, 37, 2, 1021-335X, DOI(公開)(r-map), 1100, 1106 - Anti-tumor effects of perphenazine on canine lymphoma.
Tsuji S, Yabe R, Usui T, Mizuno T, Ohama T, Sato K.
The Journal of Veterinary Medical Science
2016年09月01日, 78, 8, DOI(公開)(r-map), 1293, 1298 - Regulation of Beclin 1 Protein Phosphorylation and Autophagy by Protein Phosphatase 2A (PP2A) and Death-associated Protein Kinase 3 (DAPK3).
Fujiwara N, Usui T, Ohama T, Sato K.
The Journal of Biological Chemistry
2016年05月13日, 291, 20, DOI(公開)(r-map), 10858, 10866 - Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment
Usui T, Sakurai M, Enjoji S, Kawasaki H, Umata K, Ohama T, Fujiwara N, Yabe R, Tsuji S, Yamawaki H, Hazama S, Takenouchi H, Nakajima M, Tsunedomi R, Suzuki N, Nagano H, Sato.
Stem Cells International
2016年, DOI(公開)(r-map), 7053872 - Protein Phosphatase Methyl-Esterase PME-1 Protects Protein Phosphatase 2A from Ubiquitin/Proteasome Degradation.
Yabe R, Miura A, Usui T, Mudrak I, Ogris E, Ohama T, Sato K.
PLoS One
2015年12月, 10, 12, DOI(公開)(r-map), e0145226 - Eukaryotic elongation factor 2 kinase controls proliferation and migration of vascular smooth muscle cells.
Usui T, Nijima R, Sakatsume T, Otani K, Kameshima S, Okada M, Yamawaki H.
Acta Physiologica (Oxf).
2015年02月, 213, 2, DOI(公開)(r-map), 472, 480 - Death-associated protein kinase 3 mediates vascular structural remodelling via stimulating smooth muscle cell proliferation and migration.
Usui T, Sakatsume T, Nijima R, Otani K, Kazama K, Morita T, Kameshima S, Okada M, Yamawaki H.
Clinical Science(Lond)
2014年10月, 127, 8, DOI(公開)(r-map), 539, 548 - Brain-derived neurotrophic factor promotes angiogenic tube formation through generation of oxidative stress in human vascular endothelial cells.
Usui T, Naruo A, Okada M, Hayabe Y, Yamawaki H.
Acta Physiologica (Oxf).
2014年06月, 211, 2, DOI(公開)(r-map), 385, 394 - Zipper interacting protein kinase (ZIPK): function and signaling.
Usui T, Okada M, Yamawaki H.
Apoptosis.
2014年02月, 19, 2, DOI(公開)(r-map), 387, 391 - Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells.
Usui T, Morita T, Okada M, Yamawaki H.
Hypertension
2014年02月, 63, 2, DOI(公開)(r-map), 397, 403 - Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation.
Usui T, Okada M, Hara Y, Yamawaki H.
American Journal of Physiology-Heart and Circulatory Physiology
2013年09月01日, 305, 5, DOI(公開)(r-map), H756, H768 - Death-associated protein kinase 3 mediates vascular inflammation and development of hypertension in spontaneously hypertensive rats.
Usui T, Okada M, Hara Y, Yamawaki H.
Hypertension
2012年10月, 60, 4, DOI(公開)(r-map), 1031, 1039
研究発表、招待講演等
- 三次元オルガノイド培養法を用いたオーダーメイド獣医療の開発と創薬への応用
第 4 回医薬品毒性機序研究会
2021年12月17日, 口頭発表（招待・特別） - NASHモデルマウス由来肝臓オルガノイドの開発と創薬への応⽤
日本薬理学会年会
2021年03月08日, 口頭発表（招待・特別） - イヌ膀胱がんオルガノイド培養法を用いた新規進行性膀胱がん実験モデルの確立
日本癌学会学術集会
2019年09月27日, ポスター発表 - Establishment of a culture method of dog bladder cancer organoids
Cell symposia organoid engineering
2019年08月27日, ポスター発表 - NASHモデルマウス由来肝臓オルガノイドの作製
第46回日本毒性学会学術年会
2019年06月26日, 口頭発表（一般） - ヒト大腸エアリキッドオルガノイドモデルを用いた大腸がん研究
第92回日本薬理学会年会
2019年03月16日, シンポジウム・ワークショップ パネル（公募） - イヌ膀胱がんオルガノイド培養法の樹⽴
第92回日本薬理学会年会
2019年03月15日, 口頭発表（一般） - テーラーメイド獣医療にむけた尿由来イヌ前立腺がんオルガノイド培養法の開発
第43回日本分子生物学会年会
2018年11月29日, ポスター発表 - Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells
CMCB-2018 - BIT Congress Inc
2018年10月16日, 口頭発表（招待・特別） - 尿サンプル由来イヌ前立腺がんオルガノイド培養法の樹立
第161回日本獣医学会学術集会
2018年09月10日, 口頭発表（一般） - 三次元マウス肺がんと血管内皮細胞の共培養システムの樹立
第45回日本毒性学会学術年会
2018年07月18日, 口頭発表（一般） - Establishment of a prostate cancer organoid using the dog urine stem cells
第91回日本薬理学会年会は第18回国際薬理学・臨床薬理学会議（WCP2018）
2018年07月02日, ポスター発表 - Urine sample-derived cancer organoids enable tailor-made medicine of dog prostate cancer
EAVPT 2018: 14th International Congress of the European Association for Veterinary Pharmacology and Toxicology
2018年06月25日, 口頭発表（一般）
メディア報道
- 3D organoids unlock promising insights into lung cancer in dogs
Veterinary researchers have used organoids—three-dimensional organ-like structures grown from stem cells and tissue samples—to investigate the biological processes of lung cancer in dogs, a disease that is much rarer in our canine friends than it is in humans, but often far more deadly
PHYS ORG
自 2023年09月26日, 至 2023年09月26日 - 生命の再定義悪性中皮腫オルガノイド、イヌの胸水から作出に成功
東京農工大学、山口大学、北里大学、イスクラ産業の研究グループは、悪性中皮腫に罹患したイヌの胸水から、悪性中皮腫オルガノイドを作り出すことに成功したと紹介される。
MIT Technology Review
自 2023年04月28日, 至 2023年04月28日 - 犬のぼうこうのミニ臓器
東京農工大学の臼井達哉特任講師らは、治療の難しい犬のぼうこうがんの発症の仕組みを研究するのに役立つ「ミニ臓器」の作製に成功したと発表したことが紹介される。
日経産業新聞
自 2022年06月27日, 至 2022年06月27日 - 犬のぼうこうのミニ臓器 東京農工大、がん研究に応用
東京農工大学の臼井達哉特任講師らは、治療の難しい犬のぼうこうがんの発症の仕組みを研究するのに役立つ「ミニ臓器」の作製に成功したと発表したことが紹介される。
日本経済新聞
自 2022年06月01日, 至 2022年06月01日 - 東京農工大、尿カテーテルを使って犬正常膀胱オルガノイドの作出に成功
国立大学法人東京農工大学大学院農学研究院のモハメド・エルバダウィー訪問研究員、同大学農学部共同獣医学科の藤坂航大氏（当時 学部 6年）、同大学大学院農学府共同獣医学専攻の山本晴氏(博士課程2 年)、同大学大学院農学研究院の佐々木一昭准教授、臼井達哉特任講師らは、尿カテーテルを用いて回収した正常犬の尿中に含まれる細胞から3次元(3D)オルガノイド培養を行い、膀胱粘膜組織の特徴を再現可能な犬正常膀胱オルガノイドを作出することに成功したことが紹介される。
日本経済新聞
自 2022年05月23日, 至 2022年05月23日 - コウモリが新型コロナの感染伝播に関与していない可能性、農工大がミニ臓器で確認
東京農工大学の大松勉准教授らが、ルーセットオオコウモリの腸を再現したミニ臓器(ミニ腸)の作製に成功し、それを使用した研究の結果、ルーセットオオコウモリが新型コロナウイルス感染症(COVID-19)の感染伝播に関与していないことが示唆されたと発表したことが紹介される。
マイナビニュース／gooニュース／ニコニコニュース／BIGLOBE／exciteニュース／マピオンニュース
自 2021年11月18日, 至 2021年11月18日 - 犬や猫のがん治療を支援 東京農工大発新興が始動
東京農工大学の山本晴大学院生らが、犬の膀胱癌や猫の乳がんの治療を支援するスタートアップを立ち上げたことが紹介される。
日経産業新聞
自 2021年03月31日, 至 2021年03月31日 - Japan reveals breakthrough research on cancer
The scientists, led by Tatsuya Usui, PhD, DVM, senior assistant professor from the Laboratory of Veterinary Pharmacology at the Tokyo University of Agriculture and Technology, published their findings “Establishment of 2.5D culture model using 3D bladder cancer organoid culture” in Scientific Reports.
Bio Spectrum
自 2020年06月29日, 至 2020年06月29日 - 高速培養可能で3Dオルガノイドの特徴をもつ「2.5次元培養細胞」の作出に成功－東京農工大
東京農工大学大学院共同獣医学専攻のアミラ・アブゴマ大学院生（博士課程1年）、同大農学研究院の佐々木一昭准教授、臼井達哉特任講師らの研究チームが、膀胱がんの3次元（3D）オルガノイド培養組織から細胞を分離し、新たな培養液成分を用いてゲルフリーの2次元環境下（平面上）で高速培養が可能かつ、3Dオルガノイド培養組織の特徴を維持する新たな2.5次元培養細胞（2.5Dオルガノイド）を作出することに成功したことが紹介される。
QLifePro
自 2020年06月12日, 至 2020年06月12日 - Synthesized tumor cells help diagnose cancer and optimize treatment
The research team led by Senior Assistant Professor Tatsuya Usui from the Laboratory of Veterinary Pharmacology at the Tokyo University of Agriculture and Technology published their findings in the journal Scientific Reports on June 10th, 2020.
NEWS Medical Life Sciences
自 2020年06月10日, 至 2020年06月10日 - Organoids for the development of drugs and diagnostics for NASH
Dr Tatsuya Usui, corresponding author of the paper and Senior Assistant Professor at the Laboratory of Veterinary Pharmacology, Tokyo University of Agriculture and Technology (TUAT), Japan, concluded:
Drug Target Review
自 2020年04月03日, 至 2020年04月03日 - 「NASH」病態再現 創薬研究に寄与
臼井達哉特任講師らは山口大学などと共同で、脂肪肝の一種である「非アルコール性脂肪肝炎（NASH）」の病態を再現した小さな肝臓組織を作製したことが紹介される。
日本経済新聞／WEB
自 2020年02月24日, 至 2020年02月24日 - 非アルコール性脂肪肝炎の病態進行を再現するオルガノイド作出に成功－東京農工大ほか
東京農工大学が、病態ステージの異なる「非アルコール性脂肪肝炎」(以下、NASH)モデルマウスの肝臓組織から、NASH病態の特徴である肝線維化を再現した三次元培養組織を作出することに成功したと発表したことが紹介される。
Q Life
自 2020年02月14日, 至 2020年02月14日 - 犬の抗がん剤、尿で効果確認
東京農工大学の臼井達哉特任講師らの研究グループが、ぼうこうがんの犬の尿から、がんの細胞を短期間で増やす手法を確立したことが紹介される。
日経産業新聞
自 2019年08月01日, 至 2019年08月01日 - 膀胱がんの犬の尿から膀胱がん組織を再現、東京農工大学が成功
東京農工大学の臼井達哉特任講師らが、膀胱がん罹患犬の尿に含まれる微量ながん幹細胞から生体内の膀胱がん組織を培養ディッシュ上で再現する新たな実験モデルを確立したことが紹介される。
大学ジャーナル
自 2019年07月28日, 至 2019年07月28日 - 東京農工大、膀胱がん罹患犬の尿から膀胱がん組織の再現に成功
日経新聞電子版
自 2019年07月24日, 至 2019年07月24日
所属学協会
受賞
- 第8回 日本毒性学会技術賞
新規三次元培養法，エアリキッドインターフェイス(ALI)オルガノイド培養法の確立と毒性試験への応用
2018年06月26日 - 第31回 二宮善基記念賞
Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells
2016年06月 - 平成24年度 獣医学奨励賞
血管炎症性障害を介して高血圧症進展を制御する新規カルモジュリン関連蛋白質の探索と機能解析
2012年03月 - 第153回 日本獣医学会学術集会 大会長賞
血管炎症性障害を介して高血圧症進展を制御する新規カルモジュリン関連蛋白質の探索と機能解析
2012年03月 - 第2回 日本比較薬理学・毒性学会 奨励賞
ジヒドロピリジン系カルシウム拮抗薬CV-159の血管平滑筋細胞における抗炎症作用
2009年09月