研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

分割表示 1,287 件中 181 - 200 件目／全件表示 >>

Low temperature plasma irradiation products of sodium lactate solution that induce cell death on U251SP glioblastoma cells were identified. 査読有り国際誌 Open Access

Tanaka H, Hosoi Y, Ishikawa K, Yoshitake J, Shibata T, Uchida K, Hashizume H, Mizuno M, Okazaki Y, Toyokuni S, Nakamura K, Kajiyama H, Kikkawa F, Hori M

Scientific reports 11 巻 ( 1 ) 頁： 18488 - 18488 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Scientific Reports

Low-temperature plasma is being widely used in the various fields of life science, such as medicine and agriculture. Plasma-activated solutions have been proposed as potential cancer therapeutic reagents. We previously reported that plasma-activated Ringer’s lactate solution exhibited selective cancer-killing effects, and that the plasma-treated L-sodium lactate in the solution was an anti-tumor factor; however, the components that are generated through the interactions between plasma and L-sodium lactate and the components responsible for the selective killing of cancer cells remain unidentified. In this study, we quantified several major chemical products, such as pyruvate, formate, and acetate, in plasma-activated L-sodium lactate solution by nuclear magnetic resonance analysis. We further identified novel chemical products, such as glyoxylate and 2,3-dimethyltartrate, in the solution by direct infusion-electrospray ionization with tandem mass spectrometry analysis. We found that 2,3-dimethyltartrate exhibited cytotoxic effects in glioblastoma cells, but not in normal astrocytes. These findings shed light on the identities of the components that are responsible for the selective cytotoxic effect of plasma-activated solutions on cancer cells, and provide useful data for the potential development of cancer treatments using plasma-activated L-sodium lactate solution.

DOI： 10.1038/s41598-021-98020-w

女性器へのタルクの曝露は鉄過剰環境を形成し卵巣がんの発がんに関わる

本岡大社, 伊藤文哉, 田代浩徳, 片渕秀隆, 豊國伸哉

日本癌学会総会記事 80回巻頁： [E1 - 6] 2021年9月

BRCA1欠損は腎臓における鉄代謝の変化と酸化ストレスによる腎発がんに関わる

孔穎怡, 本岡大社, 赤塚慎也, 真下知士, 今岡達彦, 豊國伸哉

日本癌学会総会記事 80回巻頁： [P2 - 1] 2021年9月

変革する病理学:形態診断から普遍的研究プラットフォームへ実験病理学に起源を持つがんのフェロトーシス抵抗性

豊國伸哉, Zheng Hao, Kong Yingyi, Yaguang Luo, 本岡大社

日本癌学会総会記事 80回巻頁： [S10 - 6] 2021年9月

Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer. 査読有り国際誌 Open Access

Miyata K, Imai Y, Hori S, Nishio M, Loo TM, Okada R, Yang L, Nakadai T, Maruyama R, Fujii R, Ueda K, Jiang L, Zheng H, Toyokuni S, Sakata T, Shirahige K, Kojima R, Nakayama M, Oshima M, Nagayama S, Seimiya H, Hirota T, Saya H, Hara E, Takahashi A

Proceedings of the National Academy of Sciences of the United States of America 118 巻 ( 35 ) 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Proceedings of the National Academy of Sciences of the United States of America

Cellular senescence causes a dramatic alteration of chromatin organization and changes the gene expression profile of proinflammatory factors, thereby contributing to various age-related pathologies through the senescence-associated secretory phenotype (SASP). Chromatin organization and global gene expression are maintained by the CCCTC-binding factor (CTCF); however, the molecular mechanism underlying CTCF regulation and its association with SASP gene expression remains unclear. We discovered that noncoding RNA (ncRNA) derived from normally silenced pericentromeric repetitive sequences directly impairs the DNA binding of CTCF. This CTCF disturbance increases the accessibility of chromatin and activates the transcription of SASP-like inflammatory genes, promoting malignant transformation. Notably, pericentromeric ncRNA was transferred into surrounding cells via small extracellular vesicles acting as a tumorigenic SASP factor. Because CTCF blocks the expression of pericentromeric ncRNA in young cells, the down-regulation of CTCF during cellular senescence triggers the up-regulation of this ncRNA and SASP-related inflammatory gene expression. In this study, we show that pericentromeric ncRNA provokes chromosomal alteration by inhibiting CTCF, leading to a SASP-like inflammatory response in a cell-autonomous and non-cell-autonomous manner and thus may contribute to the risk of tumorigenesis during aging.

DOI： 10.1073/pnas.2025647118

Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia. 査読有り国際誌 Open Access

Miura M, Imai K, Tsuda H, Miki R, Tano S, Ito Y, Hirako-Takamura S, Moriyama Y, Ushida T, Iitani Y, Nakano-Kobayashi T, Toyokuni S, Kajiyama H, Kotani T

International journal of molecular sciences 22 巻 ( 17 ) 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Molecular Sciences

Oxidative stress plays a pathological role in pulmonary hypoplasia and pulmonary hypertension in congenital diaphragmatic hernia (CDH). This study investigated the effect of molecular hydrogen (H2), an antioxidant, on CDH pathology induced by nitrofen. Sprague-Dawley rats were divided into three groups: control, CDH, and CDH + hydrogen-rich water (HW). Pregnant dams of CDH + HW pups were orally administered HW from embryonic day 10 until parturition. Gasometric evaluation and histological, immunohistochemical, and real-time polymerase chain re-action analyses were performed. Gasometric results (pH, pO2, and pCO2 levels) were better in the CDH + HW group than in the CDH group. The CDH + HW group showed amelioration of alveo-larization and pulmonary artery remodeling compared with the CDH group. Oxidative stress (8-hydroxy-2′-deoxyguanosine-positive-cell score) in the pulmonary arteries and mRNA levels of pro-tein-containing pulmonary surfactant that protects against pulmonary collapse (surfactant protein A) were significantly attenuated in the CDH + HW group compared with the CDH group. Overall, prenatal H2 administration improved respiratory function by attenuating lung morphology and pulmonary artery thickening in CDH rat models. Thus, H2 administration in pregnant women with diagnosed fetal CDH might be a novel antenatal intervention strategy to reduce newborn mortality due to CDH.

DOI： 10.3390/ijms22179500

Role and management of oxidative stress in human disease. 査読有り国際誌 Open Access

Checker R, Sharma D, Sandur SK, Toyokuni S

Free radical research 55 巻 ( 8 ) 頁： 755 - 757 2021年8月

Non-thermal plasma-induced DMPO-OH yields hydrogen peroxide. 国際誌

Okazaki Y, Tanaka H, Matsumoto KI, Hori M, Toyokuni S

Archives of biochemistry and biophysics 705 巻頁： 108901 - 108901 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Archives of Biochemistry and Biophysics

Recent developments in electronics have enabled the medical applications of non-thermal plasma (NTP), which elicits reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as hydroxyl radical (●OH), hydrogen peroxide (H<inf>2</inf>O<inf>2</inf>), singlet oxygen (1O<inf>2</inf>), superoxide (O<inf>2</inf>●-), ozone, and nitric oxide at near-physiological temperatures. In preclinical studies or human clinical trials, NTP promotes blood coagulation, eradication of bacterial, viral and biofilm-related infections, wound healing, and cancer cell death. To elucidate the solution-phase biological effects of NTP in the presence of biocompatible reducing agents, we employed electron paramagnetic resonance (EPR) spectroscopy to quantify ●OH using a spin-trapping probe, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO); 1O<inf>2</inf> using a fluorescent probe; and O<inf>2</inf>●- and H<inf>2</inf>O<inf>2</inf> using luminescent probes in the presence of thiols or tempol. NTP-induced ●OH was significantly scavenged by dithiothreitol (DTT), reduced glutathione (GSH), and oxidized glutathione (GSSG) in 2 or 5 mM DMPO. NTP-induced O<inf>2</inf>●- was significantly scavenged by 10 μM DTT and GSH, while 1O<inf>2</inf> was not efficiently scavenged by these compounds. GSSG degraded H<inf>2</inf>O<inf>2</inf> more effectively than GSH and DTT, suggesting that the disulfide bonds reacted with H<inf>2</inf>O<inf>2</inf>. In the presence of 1–50 mM DMPO, NTP-induced H<inf>2</inf>O<inf>2</inf> quantities were unchanged. The inhibitory effect of tempol concentration (50 and 100 μM) on H<inf>2</inf>O<inf>2</inf> production was observed in 1 and 10 mM DMPO, whereas it became ineffective in 50 mM DMPO. Furthermore, DMPO-OH did not interact with tempol. These results suggest that DMPO and tempol react competitively with O<inf>2</inf>●-. Further studies are warranted to elucidate the interaction between NTP-induced ROS and biomolecules.

DOI： 10.1016/j.abb.2021.108901

Lysosomal nitric oxide determines transition from autophagy to ferroptosis after exposure to plasma-activated Ringer's lactate. 国際誌 Open Access

Jiang L, Zheng H, Lyu Q, Hayashi S, Sato K, Sekido Y, Nakamura K, Tanaka H, Ishikawa K, Kajiyama H, Mizuno M, Hori M, Toyokuni S

Redox biology 43 巻頁： 101989 - 101989 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Redox Biology

Non-thermal plasma (NTP), an engineered technology to generate reactive species, induces ferroptosis and/or apoptosis specifically in various-type cancer cells. NTP-activated Ringer's lactate (PAL) is another modality for cancer therapy at preclinical stage. Here we found that PAL induces selective ferroptosis of malignant mesothelioma (MM) cells, where non-targeted metabolome screening identified upregulated citrulline-nitric oxide (.NO) cycle as a PAL target .NO probe detected biphasic peaks transiently at PAL exposure with time-dependent increase, which was responsible for inducible .NO synthase (iNOS) overexpression through NF-κB activation. .NO and lipid peroxidation occupied lysosomes as a major compartment with increased TFEB expression. Not only ferrostatin-1 but inhibitors for .NO and/or iNOS could suppress this ferroptosis. PAL-induced ferroptosis accompanied autophagic process in the early phase, as demonstrated by an increase in essential amino acids, LC3B-II, p62 and LAMP1, transforming into the later phase with boosted lipid peroxidation. Therefore, .NO-mediated lysosomal impairment is central in PAL-induced ferroptosis.

DOI： 10.1016/j.redox.2021.101989

L-Dehydroascorbate efficiently degrades non-thermal plasma-induced hydrogen peroxide 国際誌

Okazaki Y.

Archives of Biochemistry and Biophysics 700 巻 2021年3月

Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy. 国際誌 Open Access

Nakamura K, Yoshikawa N, Mizuno Y, Ito M, Tanaka H, Mizuno M, Toyokuni S, Hori M, Kikkawa F, Kajiyama H

Cancers 13 巻 ( 5 ) 頁： 1 - 15 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancers

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The major cause of EOC’s lethality is that intraperitoneal recurrence occurs with high frequency due to occult metastasis. We had demonstrated that plasma-activated medium (PAM) exerts a metastasis-inhibitory effect on ovarian cancer in vitro and in vivo. Here we investigated how PAM inhibits intraperitoneal metastasis. We studied PAM’s inhibition of micro-dissemination onto the omentum by performing in vivo imaging in combination with a sequential histological analysis. The results revealed that PAM induced macrophage infiltration into the disseminated lesion. The iNOS-positive signal was co-localized at the macrophages in the existing lesion, indicating that PAM might induce M1-type macrophages. This may be another mechanism of the antitumor effect through a PAM-evoked immune response. Intraperitoneal lavage with plasma-activated lactate Ringer’s solution (PAL) significantly improved the overall survival rate in an ovarian cancer mouse model. Our results demonstrated the efficiency and practicality of aqueous plasma for clinical applications.

DOI： 10.3390/cancers13051141

Role of ferroptosis in carcinogenesis and tumor biology

Toyokuni Shinya

FREE RADICAL BIOLOGY AND MEDICINE 165 巻 2021年3月

Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation. 国際誌 Open Access

Omori S, Tsugita M, Hoshikawa Y, Morita M, Ito F, Yamaguchi SI, Xie Q, Noyori O, Yamaguchi T, Takada A, Saitoh T, Toyokuni S, Akiba H, Nagata S, Kinoshita K, Nakayama M

Cell reports 34 巻 ( 6 ) 頁： 108734 - 108734 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cell Reports

Needle-like multi-walled carbon nanotubes (MWCNTs) are engulfed by macrophages, which cause inflammation and asbestosis-like pathogenesis in rodents; however, how macrophages recognize MWCNTs remains unclear. Omori et al. demonstrate that Tim4 recognizes MWCNTs through aromatic-aromatic interactions and mediates macrophage phagocytosis leading to granulomas.

DOI： 10.1016/j.celrep.2021.108734

Mechanism of asbestos-induced carcinogenesis via dysregulation of redox-active iron 国際誌

Ito Fumiya, Toyokuni Shinya

CANCER SCIENCE 112 巻頁： 998 - 998 2021年2月

Mechanism of asbestos-induced carcinogenesis via dysregulation of redox-active iron 国際誌

Ito Fumiya, Toyokuni Shinya

CANCER SCIENCE 112 巻頁： 998 - 998 2021年2月

Signature analysis of genomic mutations in asbestos-induced rat mesothelioma

Akatsuka Shinya, Jiang Li, Elzawahry Asmaa, Kato Mamoru, Totsuka Yukari, Shibata Tatsuhiro, Toyokuni Shinya

CANCER SCIENCE 112 巻頁： 610 - 610 2021年2月

Asbestos and talc contribute to ovarian carcinogenesis via iron overload

Motooka Yashiro, Ito Fumiya, Tashiro Hironori, Katabuchi Hidetaka, Toyokuni Shinya

CANCER SCIENCE 112 巻頁： 245 - 245 2021年2月

Role of redox-active metals for the prevention and treatment of cancer in the era of precision medicine

Toyokuni Shinya, Richardson Des R.

CANCER SCIENCE 112 巻頁： 996 - 996 2021年2月

Defective biosynthesis of ascorbic acid in Sod1-deficient mice results in lethal damage to lung tissue 国際誌

Homma T.

Free Radical Biology and Medicine 162 巻頁： 255 - 265 2021年1月

Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma 国際誌

Yamashita K.

Genes Chromosomes and Cancer 60 巻 ( 1 ) 頁： 26 - 37 2021年1月

　前のページ - 次のページ　

<豊國 伸哉>

論文 - 豊國 伸哉

<豊國　伸哉>

論文 - 豊國　伸哉