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農家への意識調査を基したトルコにおける営農の持続性に関する経済研究 : 日本（新潟）における環境保全型農業の実践を踏まえて
Get PDF新潟大学Niigata University博士（農学）新大院博(農)第245
DDX3X mediates EGFR-TKI resistance through VEGFR signaling
Get PDF新潟大学Niigata University博士（医学）上皮成長因子受容体（Epidermal Growth Factor Receptor; EGFR）チロシンキナーゼ阻害剤（tyrosine kinase inhibitor; TKI）は、EGFR活性化変異を有する非小細胞肺癌（non-small cell lung cancer; NSCLC）に対して非常に高い治療効果を示すが、癌細胞は耐性を獲得し再発する。これまでEGFR-TKI耐性機序の検討が進められてきたが、未だ不明な部分も多い。我々は以前、マウスの悪性黒色腫細胞株に、癌幹細胞（cancer stem cell; CSC）様の特徴を有する亜集団が存在すること、これらの細胞集団はDEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X)を高発現していることを発見した。また、EGFR 遺伝子変異陽性ヒト肺癌細胞であるPC9細胞株の中にも、DDX3Xを高発現し、非接着性でCSCの特性を有する細胞集団が存在することを見出した。PC9にDDX3Xを遺伝子導入すると、EGFR-TKIへの耐性が付与された。本研究では、PC9に存在するCSCにおける、EGFR-TKI耐性機序を検討した。PC9由来のCSCでは、血管内皮細胞増殖因子受容体（vascular endothelial growth factor receptor 2; VEGFR2）の発現が増加していた。また、DDX3X遺伝子を導入したPC9細胞はEGFR-TKI単剤に抵抗性を示したが、EGFRとVEGFRシグナル伝達経路の両方を遮断すると、EGFR下流シグナルのリン酸化が減少した。加えてEGFR-TKIと VEGFR-TKIまたは抗VEGF抗体の併用療法は、EGFR遺伝子変異陽性肺癌モデルマウスの腫瘍の進行を有意に抑制した。これらの知見は、肺癌細胞内にはEGFR-TKIに耐性のCSCが存在し、DDX3Xを介してVEGFRシグナル依存性を持つこと、EGFRとVEGF伝達経路の遮断によりCSCを根絶することで、EGFR-TKIの抗腫瘍効果を高められることを示している。新大院博（医）第1171
T2WI 高信号を示す子宮平滑筋腫瘍に対するMRテクスチャー解析 : 良性の子宮筋腫と子宮平滑筋肉腫/STUMP との鑑別
Get PDF新潟大学Niigata University博士（医学）新大院博（医）第1173
日本人の心血管疾患予測に最適化されたメタボリックシンドロームの新基準の有用性
Get PDF新潟大学Niigata University博士（医学）ims: We attempted to clarify whether the multiple criteria for metabolic syndrome (MetS) can sufficiently predict cardiovascular disease, whether waist circumference (WC) should be required, and whether sex-specific thresholds for each component are necessary. Only a few large-scale studies among East Asians have addressed the ability of MetS to predict cardiovascular disease. Methods: We analyzed the data of 330,051 men and 235,028 women aged 18–74 years with no history of coronary artery disease (CAD) or cerebrovascular disease (CVD) from a nationwide Japanese claims database accumulated during 2008–2016. The association of each MetS component with CAD or CVD (CAD/CVD), MetS associated with CAD/CVD according to various criteria, and utility of modified criteria with more specific optimal values for each component were examined using multivariate Cox regression and receiver operating characteristic (ROC) analysis. Results: During the study, 3,934 men (1.19%) and 893 women (0.38%) developed CAD/CVD. For each current MetS criteria, there was a 1.3- to 2.9-fold increased risk of CAD/CVD. Optimal thresholds for predicting CAD/CVD were WCs of 83 and 77 cm, triglycerides levels of 130 and 90 mg/dl, high-density lipoprotein cholesterol levels of 50 and 65 mg/dl, blood pressures of 130/80 and 120/80 mmHg, and fasting plasma glucose levels of 100 and 90 mg/dl for men and women, respectively. The existing MetS criteria and modified criteria were not significantly different in predicting CAD/CVD, but using the modified criteria markedly increased the prevalence of MetS and percentage of people with MetS developing CAD/CVD. Conclusions: Although various criteria for MetS similarly predicted CAD/CVD, the new criteria greatly reduced the number of high-risk individuals, especially women, overlooked by the current criteria.Yurie Yamazaki, Kazuya Fujihara, Takaaki Sato, Mayuko Harada Yamada, Yuta Yaguchi, Yasuhiro Matsubayashi, Takaho Yamada, Satoru Kodama, Kiminori Kato, Hitoshi Shimano, Hirohito Sone, Usefulness of New Criteria for Metabolic Syndrome Optimized for Prediction of Cardiovascular Diseases in Japanese, Journal of Atherosclerosis and Thrombosis, 2024, Volume 31, Issue 4, Pages 382-395, Released on J-STAGE April 01, 2024, Advance online publication November 17, 2023, Online ISSN 1880-3873, Print ISSN 1340-3478, https://doi.org/10.5551/jat.64380, https://www.jstage.jst.go.jp/article/jat/31/4/31_64380/_article/-char/en新大博（医）第1197
リンパ系の濾過機能にはリンパ節のミクロあるいはマクロの解剖学的構造が不可欠である
Get PDF新潟大学Niigata University博士（医学）In the lymphatic vascular system, lymph nodes (LNs) play a pivotal role in filtering and removing lymph-borne substances. The filtering function of LNs involves resident macrophages tightly associated with unique lymphatic sinus structures. Moreover, an intermittently arranged LN in the lymphatic pathway is considered to cooperatively prevent lymph-borne substances from entering blood circulation. However, the functional significance of tissue microarchitecture, cellular composition, and individual LNs in the
“LN chain” system is not fully understood. To explore the mechanistic and histo-anatomical significance of LNs as lymph fluid filters, we subcutaneously injected fluorescent tracers into mice and examined the details of lymphatic transport to the LNs qualitatively and quantitatively. Lymph-borne tracers were selectively accumulated in the MARCO+ subcapsular-medullary sinus border (SMB) region of the LN, in which reticular lymphatic endothelial cells and CD169+F4/80+ medullary sinus macrophages construct a dense meshwork of the physical barrier, forming the main body to capture the tracers. We also demonstrated stepwise filtration via the LN chain in the lymphatic basin, which prevented tracer leakage into the blood. Furthermore, inflammatory responses that induce the remodeling of LN tissue as well as the lymphatic pathway reinforce the overall filtering capacity of the lymphatic basin. Taken together, specialized tissue infrastructure in the LNs and their systematic orchestration constitute an integrated filtering system for lymphatic recirculation.Ozawa M, Nakajima S, Kobayashi D, Tomii K, Li N-J, Watarai T, Suzuki R, Watanabe S, Kanda Y, Takeuchi A and Katakai T (2022) Micro- and Macro-Anatomical Frameworks of Lymph Nodes Indispensable for the Lymphatic System Filtering Function. Front. Cell Dev. Biol. 10:902601. doi: 10.3389/fcell.2022.902601
First publication by Frontiers in Cell and Developmental Biology新大博（医）第1828
