Updated on 2024/04/27

写真a

 
KANEMITSU Yoshitomi
 
Organization
University Medical and Dental Hospital Division of Pharmacy Associate Professor
Graduate School of Medical and Dental Sciences Molecular and Cellular Medicine Molecular Genetics Associate Professor
Title
Associate Professor
Homepage
https://omics.med.niigata-u.ac.jp/member.html
External link

Degree

  • 博士（薬学） ( 2020.9   東北大学 )

  • 修士 (薬学) ( 2011.3   東北大学 )

Research Areas

  • Life Science / Clinical pharmacy

  • Life Science / Pharmaceutical analytical chemistry and physicochemistry  / メタボロミクス/プロテオミクス

Research History (researchmap)

  • Niigata University   Medical and Dental Hospital, Division of Pharmacy   Associate Professor

    2024.4

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  • Niigata University   School of Medicine, Faculty of Medicine, Center for Research Promotion   Assistant Professor

    2023.4 - 2024.3

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  • Niigata University   Medical and Dental Hospital Clinical and Translational Research Center   Specially Appointed Assistant Professor

    2019.4 - 2023.3

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  • Tohoku University   University Hospital Pharmaceutical Sciences   Research Assistant

    2018.4 - 2019.3

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  • Tohoku University   Graduate School of Pharmaceutical Sciences   Research Assistant

    2015 - 2018.3

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  • Niigata University   Medical and Dental Hospital Division of Pharmacy

    2011 - 2014.12

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Research History

  • Niigata University   Division of Pharmacy, University Medical and Dental Hospital   Associate Professor

    2024.4

  • Niigata University   Molecular Genetics, Molecular and Cellular Medicine, Graduate School of Medical and Dental Sciences   Associate Professor

    2024.4

  • Niigata University   Institute of Medicine and Dentistry, Academic Assembly   Assistant Professor

    2023.4 - 2024.3

  • Niigata University   Molecular Genetics, Molecular and Cellular Medicine, Graduate School of Medical and Dental Sciences   Assistant Professor

    2023.4 - 2024.3

  • Niigata University   University Medical and Dental Hospital Clinical and Translational Research Center   Specially Appointed Assistant Professor

    2019.4 - 2023.3

 

Papers

  • Methylmercury directly modifies the 105th cysteine residue in oncostatin M to promote binding to tumor necrosis factor receptor 3 and inhibit cell growth. Reviewed International journal

    Takashi Toyama, Sidi Xu, Yoshitomi Kanemitsu, Takashi Hasegawa, Takuya Noguchi, Jin-Yong Lee, Atsushi Matsuzawa, Akira Naganuma, Gi-Wook Hwang

    Archives of toxicology   2023.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    We previously found that methylmercury induces expression of oncostatin M (OSM), which is released extracellularly and binds to tumor necrosis factor receptor 3 (TNFR3), possibly enhancing its own toxicity. However, the mechanism by which methylmercury causes OSM to bind to TNFR3 rather than to its known receptors, OSM receptor and LIFR, is unknown. In this study, we aimed to elucidate the effect of methylmercury modification of cysteine residues in OSM on binding to TNFR3. Immunostaining of TNFR3-V5-expressing cells suggested that methylmercury promoted binding of OSM to TNFR3 on the cell membrane. In an in vitro binding assay, OSM directly bound to the extracellular domain of TNFR3, and this binding was promoted by methylmercury. Additionally, the formation of a disulfide bond in the OSM molecule was essential for the binding of both proteins, and LC/MS analysis revealed that methylmercury directly modified the 105th cysteine residue (Cys105) in OSM. Next, mutant OSM, in which Cys105 was replaced by serine or methionine, increased the binding to TNFR3, and a similar effect was observed in immunoprecipitation using cultured cells. Furthermore, cell proliferation was inhibited by treatment with Cys105 mutant OSMs compared with wildtype OSM, and this effect was cancelled by TNFR3 knockdown. In conclusion, we revealed a novel mechanism of methylmercury toxicity, in which methylmercury directly modifies Cys105 in OSM, thereby inhibiting cell proliferation via promoting binding to TNFR3. This indicates a chemical disruption in the interaction between the ligand and the receptor is a part of methylmercury toxicity.

    DOI： 10.1007/s00204-023-03520-5

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  • SGLT‐1‐specific inhibition ameliorates renal failure and alters the gut microbial community in mice with adenine‐induced renal failure Reviewed International journal

    Hsin‐Jung Ho, Koichi Kikuchi, Daiki Oikawa, Shun Watanabe, Yoshitomi Kanemitsu, Daisuke Saigusa, Ryota Kujirai, Wakako Ikeda‐Ohtsubo, Mariko Ichijo, Yukako Akiyama, Yuichi Aoki, Eikan Mishima, Yoshiaki Ogata, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Takafumi Toyohara, Chitose Suzuki, Takehiro Suzuki, Nariyasu Mano, Yoshiteru Kagawa, Yuji Owada, Takane Katayama, Toru Nakayama, Yoshihisa Tomioka, Takaaki Abe

    Physiological Reports   9 ( 24 )   e15092   2021.12

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Sodium-dependent glucose cotransporters (SGLTs) have attracted considerable attention as new targets for type 2 diabetes mellitus. In the kidney, SGLT2 is the major glucose uptake transporter in the proximal tubules, and inhibition of SGLT2 in the proximal tubules shows renoprotective effects. On the other hand, SGLT1 plays a role in glucose absorption from the gastrointestinal tract, and the relationship between SGLT1 inhibition in the gut and renal function remains unclear. Here, we examined the effect of SGL5213, a novel and potent intestinal SGLT1 inhibitor, in a renal failure (RF) model. SGL5213 improved renal function and reduced gut-derived uremic toxins (phenyl sulfate and trimethylamine-N-oxide) in an adenine-induced RF model. Histological analysis revealed that SGL5213 ameliorated renal fibrosis and inflammation. SGL5213 also reduced gut inflammation and fibrosis in the ileum, which is a primary target of SGL5213. Examination of the gut microbiota community revealed that the Firmicutes/Bacteroidetes ratio, which suggests gut dysbiosis, was increased in RF and SGL5213 rebalanced the ratio by increasing Bacteroidetes and reducing Firmicutes. At the genus level, Allobaculum (a major component of Erysipelotrichaceae) was significantly increased in the RF group, and this increase was canceled by SGL5213. We also measured the effect of SGL5213 on bacterial phenol-producing enzymes that catalyze tyrosine into phenol, following the reduction of phenyl sulfate, which is a novel marker and a therapeutic target for diabetic kidney disease DKD. We found that the enzyme inhibition was less potent, suggesting that the change in the microbial community and the reduction of uremic toxins may be related to the renoprotective effect of SGL5213. Because SGL5213 is a low-absorbable SGLT1 inhibitor, these data suggest that the gastrointestinal inhibition of SGLT1 is also a target for chronic kidney diseases.

    DOI： 10.14814/phy2.15092

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.14814/phy2.15092

  • Global metabolomics analysis of serum from patients with Niemann-Pick disease type C Reviewed

    Anna Iwahori, Masamitsu Maekawa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka, Aya Narita, Torayuki Okuyama, Yoshikatsu Eto, Daisuke Saigusa, Nariyasu Mano

    Medical Mass Spectrometry   4 ( 1 )   1 - 11   2020.5

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  • The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease. Reviewed International journal

    Fumika Nanto-Hara, Yoshitomi Kanemitsu, Shinji Fukuda, Koichi Kikuchi, Kei Asaji, Daisuke Saigusa, Tomoyuki Iwasaki, Hsin-Jung Ho, Eikan Mishima, Takehiro Suzuki, Chitose Suzuki, Tomoya Tsukimi, Tetsuro Matsuhashi, Yoshitsugu Oikawa, Yukako Akiyama, Shigeo Kure, Yuji Owada, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association   35 ( 2 )   250 - 264   2020.2

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    BACKGROUND: Cardiorenal syndrome is a major cause of mortality in patients with chronic kidney disease (CKD). However, the involvement of detrimental humoral mediators in the pathogenesis of cardiorenal syndrome is still controversial. Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine or carnitine derived by the gut microbiota, has been linked directly with progression of cardiovascular disease and renal dysfunction. Thus, targeting TMAO may be a novel strategy for the prevention of cardiovascular disease and chronic kidney disease. METHODS: Linaclotide, a guanylate cyclase C agonist, was administered to adenine-induced renal failure (RF) mice and changes in renal function and levels of gut-derived uremic toxins, as well as the gut microbiota community, were analyzed using metabolomic and metagenomic methods to reveal its cardiorenal effect. RESULTS: Linaclotide decreased the plasma levels of TMAO at a clinically used low dose of 10 μg/kg in the adenine-induced RF mouse model. At a high concentration of 100 μg/kg, linaclotide clearly improved renal function and reduced the levels of various uremic toxins. A reduction in TMAO levels following linaclotide treatment was also observed in a choline-fed pro-atherosclerotic model. Linaclotide ameliorated renal inflammation and fibrosis and cardiac fibrosis, as well as decreased the expression of collagen I, transforming growth factor-β, galectin-3 (Gal-3) and ST2 genes. Plasma levels of Gal-3 and ST2 were also reduced. Because exposure of cardiomyocytes to TMAO increased fibronectin expression, these data suggest that linaclotide reduced the levels of TMAO and various uremic toxins and may result in not only renal, but also cardiac, fibrosis. F4/80-positive macrophages were abundant in small intestinal crypts in RF mice, and this increased expression was decreased by linaclotide. Reduced colonic claudin-1 levels were also restored by linaclotide, suggesting that linaclotide ameliorated the 'leaky gut' in RF mice. Metagenomic analysis revealed that the microbial order Clostridiales could be responsible for the change in TMAO levels. CONCLUSION: Linaclotide reduced TMAO and uremic toxin levels and could be a powerful tool for the prevention and control of the cardiorenal syndrome by modification of the gut-cardio-renal axis.

    DOI： 10.1093/ndt/gfz126

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  • Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS. Reviewed International journal

    Yoshitomi Kanemitsu, Eikan Mishima, Masamitsu Maekawa, Yotaro Matsumoto, Daisuke Saigusa, Hiroaki Yamaguchi, Jiro Ogura, Hiroki Tsukamoto, Yoshihisa Tomioka, Takaaki Abe, Nariyasu Mano

    Scientific reports   9 ( 1 )   19075 - 19075   2019.12

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    Carboxyl-containing metabolites, such as bile acids and fatty acids, have many important functions and microbiota is involved in the production of them. In the previous study, we found that the chronic kidney disease (CKD) model mice raised under germ-free conditions provided more severe renal damage than the mice with commensal microbiota. However, the precise influence by the microbiome and carboxyl-containing metabolites to the renal functions is unknown. In this study, we aimed to develop a novel chemical isotope labeling-LC-MS/MS method using the 2-picolylamine and its isotopologue and applied the analysis of effects of microbiome and CKD pathophysiology. The developed semi-quantitative method provided the high accuracy not inferior to the absolute quantification. By comparing of four groups of mice, we found that both microbiota and renal function can alter the composition and level of these metabolites in both plasma and intestine. In particular, the intestinal level of indole-3-acetic acid, short-chain fatty acids and n-3 type of polyunsaturated fatty acid, which play important roles in the endothelial barrier function, were significantly lower in germ-free conditions mice with renal failure. Accordingly, it is suggested these metabolites might have a renoprotective effect on CKD by suppressing epithelial barrier disruption.

    DOI： 10.1038/s41598-019-55600-1

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  • Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. Reviewed International journal

    Koichi Kikuchi, Daisuke Saigusa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Paxton Thanai, Naoto Suzuki, Koki Mise, Hiroaki Yamaguchi, Tomohiro Nakamura, Kei Asaji, Chikahisa Mukawa, Hiroki Tsukamoto, Toshihiro Sato, Yoshitsugu Oikawa, Tomoyuki Iwasaki, Yuji Oe, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Fumika Nanto-Hara, Jiro Ogura, Ritsumi Saito, Shizuko Nagao, Yusuke Ohsaki, Satoshi Shimada, Takehiro Suzuki, Takafumi Toyohara, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yukako Akiyama, Mariko Ichijo, Tetsuro Matsuhashi, Akihiro Matsuo, Yoshiaki Ogata, Ching-Chin Yang, Chitose Suzuki, Matthew C Breeggemann, Jurgen Heymann, Miho Shimizu, Susumu Ogawa, Nobuyuki Takahashi, Takashi Suzuki, Yuji Owada, Shigeo Kure, Nariyasu Mano, Tomoyoshi Soga, Takashi Wada, Jeffrey B Kopp, Shinji Fukuda, Atsushi Hozawa, Masayuki Yamamoto, Sadayoshi Ito, Jun Wada, Yoshihisa Tomioka, Takaaki Abe

    Nature communications   10 ( 1 )   1835 - 1835   2019.4

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    Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

    DOI： 10.1038/s41467-019-09735-4

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  • Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model Reviewed International journal

    †Mishima, E, †Fukuda, S, Contributed equally to this work, Kanemitsu, Y, Saigusa, D, Mukawa, C, Asaji, K, Matsumoto, Y, Tsukamoto, H, Tachikawa, T, Tsukimi, T, Fukuda, N, Ho, HJ., Kikuchi, K. Suzuki, C, Nanto, F, Suzuki, T, Ito, S, Soga, T, Tomioka, Y, Abe, T

    Am. J. Physiol. Renal. Physiol.   315 ( 4 )   F824-F833 - F833   2018.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Journal of Physiology - Renal Physiology  

    © 2018 the American Physiological Society. Mishima E, Fukuda S, Kanemitsu Y, Saigusa D, Mukawa C, Asaji K, Matsumoto Y, Tsukamoto H, Tachikawa T, Tsukimi T, Fukuda NN, Ho HJ, Kikuchi K, Suzuki C, Nanto F, Suzuki T, Ito S, Soga T, Tomioka Y, Abe T. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. Am J Physiol Renal Physiol 315: F824–F833, 2018. First published November 22, 2017; doi:10.1152/ajprenal.00314.2017.—Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins, including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg po) treatment did not influence the impaired renal

    DOI： 10.1152/ajprenal.00314.2017

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  • Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation. Reviewed International journal

    Tsukamoto H, Takeuchi S, Kubota K, Kobayashi Y, Kozakai S, Ukai I, Shichiku A, Okubo M, Numasaki M, Kanemitsu Y, Matsumoto Y, Nochi T, Watanabe K, Aso H, Tomioka Y

    The Journal of biological chemistry   293 ( 26 )   10186 - 10201   2018.6

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    Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NF-κB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway.

    DOI： 10.1074/jbc.M117.796631

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  • The Disease-modifying Drug Candidate, SAK3 Improves Cognitive Impairment and Inhibits Amyloid beta Deposition in App Knock-in Mice. Reviewed International journal

    Hisanao Izumi, Yasuharu Shinoda, Takashi Saito, Takaomi C Saido, Keita Sato, Yasushi Yabuki, Yotaro Matsumoto, Yoshitomi Kanemitsu, Yoshihisa Tomioka, Nona Abolhassani, Yusaku Nakabeppu, Kohji Fukunaga

    Neuroscience   377   87 - 97   2018.5

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    Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of elderly dementia in the world. At present, acetylcholine inhibitors, such as donepezil, galantamine and rivastigmine, are used for AD therapy, but the therapeutic efficacy is limited. We recently proposed T-type voltage-gated Ca2+ channels' (T-VGCCs) enhancer as a new therapeutic candidate for AD. In the current study, we confirmed the pharmacokinetics of SAK3 in the plasma and brain of mice using ultra performance liquid chromatography-tandem mass spectrometry. We also investigated the effects of SAK3 on the major symptoms of AD, such as cognitive dysfunction and amyloid beta (Aβ) accumulation, in AppNL-F knock-in (NL-F) mice, which have been established as an AD model. Chronic SAK3 (0.5 mg/kg/day) oral administration for 3 months from 9 months of age improved cognitive function and inhibited Aβ deposition in 12-month-old NL-F mice. Using microarray and real-time PCR analysis, we discovered serum- and glucocorticoid-induced protein kinase 1 (SGK1) as one of possible genes involved in the inhibition of Aβ deposition and improvement of cognitive function by SAK3. These results support the idea that T-VGCC enhancer, SAK3 could be a novel candidate for disease-modifying therapeutics for AD.

    DOI： 10.1016/j.neuroscience.2018.02.031

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  • Generation and Characterization of Anti-phenyl Sulfate Monoclonal Antibodies and a Potential Use for Phenyl Sulfate Analysis in Human Blood. Reviewed

    Kanemitsu Y, Tsukamoto H, Matsumoto Y, Nozawa-Kumada K, Kondo Y, Abe T, Tomioka Y

    Biological & pharmaceutical bulletin   41 ( 8 )   1170 - 1177   2018

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    Patients with chronic kidney disease (CKD) have increased blood levels of phenyl sulfate (PS), a circulating uremic toxin. In this study, we produced anti-PS monoclonal antibodies (mAbs) and characterized their cross-reactivity to structural PS analogs. To induce PS-specific mAbs, we synthesized 4-mercaptophenyl sulfate with a sulfhydryl group at the para-position of PS and conjugated it to carrier proteins via bifunctional linkers. Using these PS conjugates as immunogens and as antigens for enzyme-linked immunosorbent assay (ELISA) screening, we produced by a hybridoma method two novel mAbs (YK33.1 and YKS19.2) that react with PS conjugates independent of carrier and linker structures. Although all of the PS analogs tested, with the exception of indoxyl sulfate, were cross-reactive to both mAbs in phosphate buffered saline (PBS), PS specificity for YKS19.2 was enhanced in human plasma and serum. YKS19.2 mAb was cross-reactive only with o-cresyl sulfate, which is absent in human blood. PS sensitivity for YKS19.2 mAb increased to an IC50 of 10.4 µg/mL when 0.1% Tween 20 was added in a primary competitive reaction. To explore potential clinical applications, we determined concentrations of PS in serum samples from 19 CKD patients by inhibition ELISA using YKS19.2 mAb and compared them to those found using an LC-MS/MS method. A good correlation was observed between each value (R2=0.825). Therefore, the unique antigen specificity of YKS19.2 mAb could be useful for prescreening of patients with accumulated PS or for comprehensive analysis of uremic toxins that have a PS-like structure.

    DOI： 10.1248/bpb.b17-00925

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  • Simultaneous quantitative analysis of uremic toxins by LC MS/MS with a reversed-phase/cation-exchange/anion-exchange tri-modal mixed-mode column Reviewed

    Yoshitomi Kanemitsu, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Daisuke Saigusa, Chikahisa Mukawa, Tatsuki Tachikawa, Takaaki Abe, Yoshihisa Tomioka

    JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES   1068   1 - 8   2017.11

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

    Column choice is crucial to the development of liquid chromatography/tandem mass spectrometry (LC-MS/MS) methods because analyte selectivity is dependent on the nature of the stationary phase. Recently, mixed-mode chromatography, which employs a combination of two or more stationary phases and solvent systems, has emerged as an alternative to multiple, complementary, single-column systems. This report describes the development and validation of a novel analytical method based on LC-MS/MS employing a reversed-phase/cation-exchange/anion-exchange tri-modal column (Scherzo SS-C18; Imtakt) for the simultaneous quantification of various uremic toxins (UTx), including creatinine, 1-methyladenosine, trimethylamine-N-oxide, indoxyl sulfate, p-cresyl sulfate, phenyl sulfate and 4-ethylphenyl sulfate. Stable isotope-labeled compounds were prepared as internal standards (ISs) for each analyte. Mobile phase optimization and appropriate gradient conditions resulted in satisfactory retention and peak resolution that could not have been attained with a single stationary phase LC system. The essential validation parameters, including intra- and inter-assay precision and accuracy, were adequate. The validated method was applied to measure serum levels of the aforementioned compounds in 19 patients with chronic kidney disease. This is the first report detailing the simultaneous quantification of these analytes using stable isotopes as ISs. Our results suggest that Scherzo SS-C18 columns will be considered breakthrough tools in the development of analytical methods for compounds that are difficult to quantify simultaneously in traditional LC systems.

    DOI： 10.1016/j.jchromb.2017.10.009

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  • Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach Reviewed

    Eikan Mishima, Shinji Fukuda, Chikahisa Mukawa, Akinori Yuri, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yasutoshi Akiyama, Noriko N. Fukuda, Hiroki Tsukamoto, Kei Asaji, Hisato Shima, Koichi Kikuchi, Chitose Suzuki, Takehiro Suzuki, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe

    KIDNEY INTERNATIONAL   92 ( 3 )   634 - 645   2017.9

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

    Gut microbiota is involved in the metabolism of uremic solutes. However, the precise influence of microbiota to the retention of uremic solutes in CKD is obscure. To clarify this, we compared adenine-induced renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining the metabolite profiles of plasma, feces, and urine using a capillary electrophoresis time-of-flight mass spectrometry-based approach. Mice with renal failure under germ-free conditions demonstrated significant changes in plasma metabolites. Among 183 detected solutes, plasma levels of 11 solutes, including major uremic toxins, were significantly lower in germ-free mice than in SPF mice with renal failure. These 11 solutes were considered microbiota-derived uremic solutes and included indoxyl sulfate, p-cresyl sulfate, phenyl sulfate, cholate, hippurate, dimethylglycine, gamma-guanidinobutyrate, glutarate, 2-hydroxypentanoate, trimethylamine N-oxide, and phenaceturate. Metabolome profiling showed that these solutes were classified into three groups depending on their origins: completely derived from microbiota (indoxyl sulfate, p-cresyl sulfate), derived from both host and microbiota (dimethylglycine), and derived from both microbiota and dietary components (trimethylamine N-oxide). Additionally, germ-free renal failure conditions resulted in the disappearance of colonic short-chain fatty acids, decreased utilization of intestinal amino acids, and more severe renal damage compared with SPF mice with renal failure. Microbiota-derived short-chain fatty acids and efficient amino acid utilization may have a renoprotective effect, and loss of these factors may exacerbate renal damage in germ-free mice with renal failure. Thus, microbiota contributes substantially to the production of harmful uremic solutes, but conversely, growth without microbiota has harmful effects on CKD progression.

    DOI： 10.1016/j.kint.2017.02.011

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  • An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody. Reviewed International journal

    Tsukamoto H, Yamagata Y, Ukai I, Takeuchi S, Okubo M, Kobayashi Y, Kozakai S, Kubota K, Numasaki M, Kanemitsu Y, Matsumoto Y, Tomioka Y

    FEBS letters   591 ( 18 )   2953 - 2953   2017.9

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    DOI： 10.1002/1873-3468.12837

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  • An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody Reviewed

    Hiroki Tsukamoto, Yuki Yamagata, Ippo Ukai, Shino Takeuchi, Misaki Okubo, Yohei Kobayashi, Sao Kozakai, Kanae Kubota, Muneo Mumasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka

    FEBS LETTERS   591 ( 16 )   2406 - 2416   2017.8

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

    Lipopolysaccharide (LPS)-induced activation of Toll-like receptor 4 (TLR4) elicits the innate immune response and can trigger septic shock if excessive. Two antibodies (HT4 and HT52) inhibit LPS-induced human TLR4 activation via novel LPS binding-independent mechanisms. The HT52 epitope resides on leucine-rich repeat 2 (LRR2) and is a feature of many inhibitory antibodies; antigen specificity of HT4 does not reside in LRR2. Here, we identified an HT4 epitope on LRR13 located close to the TLR4 dimerization interface that plays a role in NF kappa B activation. HT4 and HT52 mutually enhanced TLR4 inhibition. LRR13 is a novel inhibitory epitope and may be useful for developing anti-TLR4 antibodies. Combination therapy with LRR2 and LRR13 may effectively inhibit TLR4 activation.

    DOI： 10.1002/1873-3468.12768

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  • Rapid and selective simultaneous quantitative analysis of modified nucleosides using multi-column liquid chromatography-tandem mass spectrometry Reviewed

    Daisuke Jinno, Yoshitomi Kanemitsu, Kazuki Saitoh, Shinnosuke Nankumo, Hiroki Tsukamoto, Yotaro Matsumoto, Takaaki Abe, Yoshihisa Tomioka

    Journal of Analytical Science and Technology   1 ( 8 )   1 - 9   2017.1

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  • A case of anaphylaxis in the pediatric patient with milk allergy due to traces of Milk Protein in the lactose used as an excipient of Inavir® Inhalation Reviewed

    Miki Morikawa, Yoshitomi Kanemitsu, Hiroki Tsukamoto, Akimasa Morikawa, Yoshihisa Tomioka

    Japanese Journal of Allergology   65 ( 3 )   200 - 205   2016

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    Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

    The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir® (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir® inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir® inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as β-lactoglobulin (β-LG) by Western blotting using specific monoclonal antibody and patient's sera. The β-LG in Inavir® was supposed to be glycosylated with lactose because the molecular weight was slightly higher than β-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of β-LG contaminated in the lactose excipient of Inavir® could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients.

    DOI： 10.15036/arerugi.65.200

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  • SLC10A4 is a protease-activated transporter that transports bile acids Reviewed

    Takuya Abe, Yoshitomi Kanemitu, Masateru Nakasone, Ichiro Kawahata, Tohru Yamakuni, Akira Nakajima, Naoto Suzuki, Masazumi Nishikawa, Takanori Hishinuma, Yoshihisa Tomioka

    JOURNAL OF BIOCHEMISTRY   154 ( 1 )   93 - 101   2013.7

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    SLC10A4 belongs to the sodium bile acid cotransporter family, but has no transport activity for bile acids. We performed multiple amino acid alignments and examined the relationships between the SLC10 proteins. The extracellular N-terminus of SLC10A4 was predicted to be relatively longer at the amino acid level than those of SLC10A1, SLC10A2 and SLC10A6. We examined the relationship between the N-terminus and transport activity of SLC10A4. Rat Slc10a4 is predominantly expressed in rat cholinergic neurons; therefore, TE671 cells expressing the acetylcholine receptor and acetylcholinesterase were used. After thrombin treatment, western blotting and immunofluorescence staining demonstrated that the N-terminus of SLC10A4 might be cleaved. Substrates were added to the cells, and their uptake was quantified by liquid chromatography tandem mass spectrometry. Lithocholic acid (LCA) and taurocholic acid (TCA) uptake and cell death effects of LCA were increased by thrombin treatment. After RNA interference treatment for SLC10A4, bile acid uptake was also quantified. In consequence, increases in the LCA and TCA uptake did not occur. Therefore, SLC10A4 may have low activity but becomes activated by proteases, including thrombin, following cleavage. We have demonstrated that SLC10A4 appears to be a protease-activated transporter and transports bile acids.

    DOI： 10.1093/jb/mvt031

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  • Determination of Asymmetric Dimethylarginine and Symmetric Dimethylarginine in Biological Samples of Mice Using LC/MS/MS Reviewed

    Daisuke Saigusa, Mai Takahashi, Yoshitomi Kanemitsu, Ayako Ishida, Takaaki Abe, Tohru Yamakuni, Naoto Suzuki, Yoshihisa Tomioka

    American Journal of Analytical Chemistry   02 ( 03 )   303 - 313   2011

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    DOI： 10.4236/ajac.2011.23038

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    Other Link： http://www.scirp.org/journal/doi.aspx?DOI=10.4236/ajac.2011.23038

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  • 血液透析導入期における血中腸内細菌由来尿毒素の解析

    豊原 敬文, 山本 多恵, 金光 祥臣, 菊地 晃一, 渡邉 駿, 鈴木 健弘, 田中 哲洋, 阿部 高明

    日本透析医学会雑誌   56 ( Suppl.1 )   653 - 653   2023.5

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  • 【How to 編】臨床研究を始める前に~規制と倫理を正しく理解する

    金光祥臣

    日本医療薬学会年会講演要旨集(Web)   32   2022

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  • 医師主導治験:ポリグルタミン病に対する蛋白質凝集阻害薬の第II相試験

    石原智彦, 金光祥臣, 他田正義, 他田正義, 池中健介, 高橋祐二, 横田隆徳, 石川欽也, 平野牧人, 永井義隆, 小野寺理

    日本神経学会学術大会プログラム・抄録集   63rd   2022

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  • A trans-omic analysis on the mechanism of metabolic shift in metformin-treated immune cells

    日本分子生物学会年会プログラム・要旨集(Web)   45th   2022

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  • 血液透析とオンライン血液濾過透析による血中フェノール誘導体,核酸除去率の比較

    島 久登, 道脇 宏行, 三島 英換, 金光 祥臣, 富岡 佳久, 岡田 一義, 阿部 高明, 水口 潤

    日本透析医学会雑誌   54 ( Suppl.1 )   457 - 457   2021.5

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  • 「腸腎連関」 解明を指向した分析手法の構築と応用 Invited

    金光 祥臣

    第2回 日本質量分析学会 東北談話会要旨集   2020.10

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  • 糖尿病性腎症の発症・進展予測マーカーとしてのフェニル硫酸の有用性

    菊地 晃一, 三枝 大輔, 金光 祥臣, 松本 洋太郎, 三瀬 広記, 中村 智洋, 三島 英換, 豊原 敬文, 鈴木 健弘, 寳澤 篤, 和田 淳, 富岡 佳久, 阿部 高明

    日本腎臓学会誌   62 ( 4 )   276 - 276   2020.7

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  • アデニン誘発腎不全マウスにおけるエロビキシバットの効果

    秋山 由雅子, 前川 正充, 金光 祥臣, 菊地 晃一, 何 欣蓉, 三島 英換, 鈴木 健弘, 一條 真梨子, 鈴木 千登世, 眞野 成康, 富岡 佳久, 阿部 高明

    日本腎臓学会誌   62 ( 4 )   337 - 337   2020.7

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  • 血液透析とオンライン血液濾過透析による血中フェノール誘導体、核酸除去率の検討

    島 久登, 道脇 宏行, 金光 祥臣, 三島 英換, 鈴木 千登世, 田尾 知浩, 岡田 一義, 富岡 佳久, 阿部 高明, 水口 潤

    日本腎臓学会誌   62 ( 4 )   351 - 351   2020.7

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  • フェニル硫酸は糖尿病性腎症におけるアルブミン尿増悪の新たな原因物質である

    菊地 晃一, 三枝 大輔, 金光 祥臣, 松本 洋太郎, 三瀬 広記, 鈴木 健弘, 寳澤 篤, 和田 淳, 富岡 佳久, 阿部 高明

    日本内分泌学会雑誌   95 ( 4 )   1620 - 1620   2020.2

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  • グアニル酸シクラーゼC受容体作動薬リナクロチドは血中TMAO値を低下させ慢性腎不全に伴う心血管疾患のリスクを緩和する

    原 文香, 金光 祥臣, 福田 真嗣, 菊地 晃一, 何 欣蓉, 鈴木 千登世, 曽我 朋義, 富岡 佳久, 阿部 高明

    日本内分泌学会雑誌   95 ( 4 )   1612 - 1612   2020.2

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  • グローバルメタボロミクスによるニーマンピック病C型患者血液に特徴的なピーク探索

    前川正充, 前川正充, 岩堀杏南, 金光祥臣, 三枝大輔, 三枝大輔, 山口浩明, 山口浩明, 山口浩明, 眞野成康, 眞野成康

    JSBMS Letters   44 ( Supplement )   79 - 79   2019.8

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  • 透析におけるルビプロストンの尿毒素に対する効果

    尾形佳昭, 金井秀明, 金塚完, 中嶋俊之, 鈴木千登世, 淺地圭, 金光祥臣, 松本洋太郎, 富岡佳久, 阿部高明

    日本腎臓学会誌   61 ( 3 )   381 - 381   2019.5

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  • グアニル酸シクラーゼC受容体作動薬リナクロチドは慢性腎不全に伴う心血管疾患のリスクを緩和する

    原 文香[南都], 金光 祥臣, 福田 真嗣, 何 欣蓉, 菊地 晃一, 鈴木 千登世, 曽我 朋義, 富岡 佳久, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌   61 ( 3 )   312 - 312   2019.5

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  • 透析患者の母乳哺育の可能性 母乳内尿毒素と栄養素の解析

    遠藤 知美, 横井 秀基, 森 慶太, 長尾 早枝子, 池田 嘉宏, 廣瀬 潤子, 金光 祥臣, 金子 一成, 阿部 高明, 塚本 達雄, 柳田 素子

    日本腎臓学会誌   61 ( 3 )   381 - 381   2019.5

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  • ケモカインレセプターCCR10阻害薬による腎不全抑制効果の検討

    一條 真梨子, 何 欣蓉, 金光 祥臣, 菊地 晃一, 秋山 由雅子, 三島 英換, 鈴木 健弘, 鈴木 千登世, 富岡 佳久, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌   61 ( 3 )   325 - 325   2019.5

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  • 透析患者の母乳哺育の可能性 母乳内尿毒素と栄養素の解析

    遠藤 知美, 横井 秀基, 森 慶太, 長尾 早枝子, 池田 嘉宏, 廣瀬 潤子, 金光 祥臣, 金子 一成, 阿部 高明, 塚本 達雄, 柳田 素子

    日本小児腎臓病学会雑誌   32 ( 1Suppl. )   123 - 123   2019.5

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  • 胆汁酸トランスポーター阻害薬エロビキシバットによる腎保護作用の検討

    秋山 由雅子, 何 欣蓉, 金光 祥臣, 前川 正充, 菊地 晃一, 鈴木 健弘, 三島 英換, 一條 真梨子, 鈴木 千登世, 眞野 成康, 富岡 佳久, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌   61 ( 3 )   403 - 403   2019.5

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  • 腸内細菌由来のフェニル硫酸は糖尿病性腎臓病でのアルブミン尿増悪の原因物質かつ予測マーカーである

    菊地晃一, 三枝大輔, 金光祥臣, 松本洋太郎, 中村智洋, 淺地圭, 三瀬広記, 何欣蓉, 三島英換, 鈴木健弘, 和田淳, 寶澤篤, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌   61 ( 3 )   312 - 312   2019.5

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  • グアニル酸シクラーゼC受容体作動薬リナクロチドは腎不全に伴う腸内環境悪性化を改善し腎線維化を抑制する

    南都文香, 福田真嗣, 金光祥臣, 三枝大輔, 菊地晃一, 何欣蓉, 三島英換, 鈴木健弘, 松橋徹郎, 及川義嗣, 鈴木千登世, 富岡佳久, 曽我朋義, 伊藤貞嘉, 阿部高明

    日本腎臓学会誌   60 ( 3 )   463 - 463   2018.4

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  • グアニル酸シクラーゼC受容体作動薬リナクロチドは腎不全に伴う腸内環境悪性化を改善し腎線維化を抑制する

    南都 文香, 福田 真嗣, 金光 祥臣, 三枝 大輔, 菊地 晃一, 何 欣蓉, 三島 英換, 鈴木 健弘, 松橋 徹郎, 及川 義嗣, 鈴木 千登世, 富岡 佳久, 曽我 朋義, 伊藤 貞嘉, 阿部 高明

    日本腎臓学会誌   60 ( 3 )   463 - 463   2018.4

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  • LPS-binding proteinはリポ多糖によるCD14依存的Toll様受容体4内在化を媒介し、TRIFシグナルを制御する

    塚本 宏樹, 武内 偲乃, 久保田 佳苗, 小坂井 沙緒, 紫竹 歩, 鵜飼 一歩, 小林 洋平, 大久保 美咲, 沼崎 宗夫, 金光 祥臣, 松本 洋太郎, 野地 智法, 渡邊 康一, 麻生 久, 富岡 佳久

    生命科学系学会合同年次大会   2017年度   [2LBA - 013]   2017.12

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  • LPS‐binding proteinはリポ多糖によるCD14依存的Toll様受容体4内在化を媒介しTRIFシグナルを制御する

    塚本宏樹, 武内偲乃, 久保田佳苗, 小坂井沙緒, 紫竹歩, 鵜飼一歩, 小林洋平, 大久保美咲, 沼崎宗夫, 金光祥臣, 松本洋太郎, 野地智法, 渡邊康一, 麻生久, 富岡佳久

    日本生化学会大会(Web)   90th   ROMBUNNO.2LBA‐013 (WEB ONLY) - 013]   2017.12

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  • LPS-binding proteinはToll様受容体4の二量体化・内在化を介してTRIF依存的IKKε/TBK1/IRF3経路を活性化する

    久保田 佳苗, 武内 偲乃, 鵜飼 一歩, 小坂井 沙緒, 金光 祥臣, 松本 洋太郎, 塚本 宏樹, 富岡 佳久

    日本薬学会年会要旨集   137年会 ( 3 )   76 - 76   2017.3

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  • ヒトToll様受容体4活性化に必要なleucine-rich repeat 13は抑制抗体によって認識される

    山形 由貴, 大久保 美咲, 鵜飼 一歩, 金光 祥臣, 松本 洋太郎, 塚本 宏樹, 富岡 佳久

    日本薬学会年会要旨集   137年会 ( 3 )   142 - 142   2017.3

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  • 異なるシグナル誘導活性を持つToll様受容体4刺激抗体による抗原特異的抗体産生抑制効果

    小林 洋平, 小坂井 沙緒, 久保田 佳苗, 武内 偲乃, 金光 祥臣, 松本 洋太郎, 塚本 宏樹, 富岡 佳久

    日本薬学会年会要旨集   137年会 ( 3 )   138 - 138   2017.3

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  • LC-MSを用いた細胞内サイクリックADPリボース高感度定量法の構築

    齋藤 一樹, 金光 祥臣, 田中 晃佑, 鈴木 千登世, 阿部 高明, 塚本 宏樹, 松本 洋太郎, 富岡 佳久

    日本薬学会年会要旨集   137年会 ( 2 )   246 - 246   2017.3

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  • サイクリックADPリボース安定同位体の合成

    齋藤 一樹, 田中 晃佑, 鈴木 千登世, 阿部 高明, 金光 祥臣, 塚本 宏樹, 松本 洋太郎, 富岡 佳久

    日本薬学会年会要旨集   137年会 ( 2 )   156 - 156   2017.3

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  • LC‐HDMSおよびIMSを用いたヒト肝癌組織メタボロミクスによる新規バイオマーカーの同定

    永井滉士, 三枝大輔, 三枝大輔, 山崎貴広, 金光祥臣, 塚本宏樹, 池田均, 矢冨裕, 松本洋太郎, 富岡佳久

    日本薬学会東北支部大会講演要旨集   56th   58   2017

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  • Toll様受容体4シグナルによるGr1<sup>+</sup>CD11b<sup>+</sup>細胞誘導を介した抗原特異的抗体産生抑制機序

    小坂井沙緒, 小林洋平, 金光祥臣, 松本洋太郎, 塚本宏樹, 富岡佳久

    日本薬学会年会要旨集(CD-ROM)   137th ( 3 )   ROMBUNNO.26X‐am02S - 77   2017

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  • ミックスドモードODSカラムを用いたLC‐MS/MSによる尿毒症物質一斉定量系の構築

    金光祥臣, 淺地圭, 松本洋太郎, 塚本宏樹, 三枝大輔, 阿部高明, 富岡佳久

    日本薬学会東北支部大会講演要旨集   56th   58   2017

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  • 不活性型二量体構造の誘導を介した抑制型ヒトToll様受容体4抗体の新規作用機序

    山形由貴, 鵜飼一歩, 金光祥臣, 小林洋平, 松本洋太郎, 塚本宏樹, 富岡佳久

    日本薬学会年会要旨集(CD-ROM)   137th ( 3 )   ROMBUNNO.25X‐pm03S - 64   2017

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  • イナビル添加乳糖中のβ-ラクトグロブリンおよびその糖鎖付加体が原因と推察されたアナフィラキシーの1例

    森川 みき, 金光 祥臣, 塚本 宏樹, 森川 昭正, 富岡 佳久

    アレルギー   65 ( 3 )   200 - 205   2016.5

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    Language：Japanese   Publisher：(一社)日本アレルギー学会  

    症例は,牛乳アレルギーおよび気管支喘息既往歴を有する6歳女児.インフルエンザB型に罹患し,ラニナミビルオクタン酸エステル水和物吸入粉末剤(イナビル)を使用後にアナフィラキシーを起こした.プリックテスト並びに薬剤刺激好塩基球活性化試験を実施したところ,イナビルと添加剤の乳糖水和物に陽性を示し,ラニナミビルオクタン酸エステル水和物は陰性を示した.本症例では,添加剤の乳糖に夾雑する乳タンパク質がアレルゲンとなった可能性が考えられ,その同定を試みた.ウェスタンブロット(WB)により,添加剤の乳糖水和物中からβ-ラクトグロブリン(β-LG)が検出され,その分子量およびin vitro実験の結果から糖鎖付加体であると推定した.さらに患者血清を用いたWBの結果から,本症例のアレルゲンが,糖鎖付加されたβ-LGである可能性が高いと判断した.本研究は,吸入粉末製剤の添加剤乳糖が乳アレルギーを起こす危険性を示す結果となった.本症例のようなインフルエンザ患者は,気道過敏性が亢進しているため特に注意が必要である.(著者抄録)

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  • リスクマネジメント 院内での薬剤師の活動 がん化学療法施行患者の持参薬による副作用発現への介入 病棟薬剤師による持参薬の薬学的管理の重要性

    金光 祥臣, 外山 聡, 佐藤 博

    医薬ジャーナル   50 ( 6 )   1605 - 1610   2014.6

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    Language：Japanese   Publisher：(株)医薬ジャーナル社  

    入院時に患者が持ち込む持参薬は、入院前は服用が継続できており、また、担当医の専門領域外の薬剤であることも多いため、その副作用が新規プロブレムとして抽出され難い場合がある。特に、病態変化や薬剤による腎・肝障害は、薬物動態に影響を及ぼすため、注意を要する。このような場面では、病棟薬剤師が担当医へ積極的に情報提供し、処方提案を行うことが重要となる。今回、抗がん剤治療施行後に、持参薬の薬物動態の変動が原因で副作用の発現が疑われた2例に対して、薬剤師の介入後、症状の改善が認められた例を紹介する。これらの介入を通じて、病棟薬剤師による持参薬を含めた薬学的管理が、リスクマネジメントの観点から重要であることが再認識された。(著者抄録)

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  • 胆汁酸トランスポーターSLC10A4の機能解析

    阿部 拓哉, 金光 祥臣, 中曽根 正皓, 川畑 伊知郎, 山國 徹, 中島 晶, 鈴木 直人, 西川 正純, 菱沼 隆則, 富岡 佳久

    日本薬学会年会要旨集   132年会 ( 4 )   271 - 271   2012.3

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    Language：Japanese   Publisher：(公社)日本薬学会  

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  • LC/MS/MSを用いたOATP1B3の絶対定量と過剰発現細胞のプロテオーム解析

    金光祥臣, 阿部拓哉, 中曽根正皓, 三枝大輔, 菱沼隆則, 鈴木直人, 富岡佳久

    日本薬学会年会要旨集   131st ( 4 )   2011

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  • ヒト小脳由来TE671細胞におけるプロテアーゼ活性化トランスポーターの機能解析

    阿部拓哉, 中島晶, 金光祥臣, 三枝大輔, 鈴木直人, 富岡佳久, 菱沼隆則

    日本薬学会年会要旨集   131st ( 4 )   2011

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  • LC/MS/MSを用いたADMA及びSDMA分離分析系の構築並びに化合物生体組織分布の解明

    高橋舞, 三枝大輔, 石田綾子, 芝可奈子, 金光祥臣, 有馬直明, 濱弘太郎, 山國徹, 青木淳賢, 鈴木直人, 富岡佳久

    日本薬学会東北支部大会講演要旨集   50th   2011

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  • 地域薬局における慢性腎臓病に対する食での取り組み

    崎野健一, 崎野健一, 尾崎敦子, 尾形みなみ, 小林満, 岩倉大介, 星友典, 金光祥臣, 山岸祐輔, 三枝大輔, 山家靖, 山家靖, 鈴木直人, 大野武, 大野武, 富岡佳久

    日本薬学会年会要旨集   131st ( 4 )   2011

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  • 大学院生の薬剤師研修を通じた医師への処方支援

    三村享, 松本周平, 金光祥臣, 村井ユリ子, 村井ユリ子, 久道周彦, 佐藤真由美, 鈴木直人, 齊藤直美, 土屋雅美, 木皿重樹, 三枝大輔, 眞野成康, 眞野成康, 富岡佳久

    日本薬学会年会要旨集   130th ( 4 )   2010

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  • 次世代型専門薬剤師育成を目指した大学院教育プログラムの開発-がん化学療法処方設計支援基礎実習カリキュラムの構築

    鈴木直人, 金光祥臣, 松本周平, 三村享, 三枝大輔, 村井ユリ子, 村井ユリ子, 久道周彦, 佐藤真由美, 齊藤直美, 木皿重樹, 眞野成康, 眞野成康, 富岡佳久

    日本薬学会年会要旨集   130th ( 4 )   2010

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Industrial property rights

  • 抗硫酸フェニル誘導体抗体

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    Application no：特願2016-252157  Date applied：2016.12

    Announcement no：特開2018-102211  Date announced：2018.7

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Awards

  • 第 26 回日本医療薬学会年会 優秀演題賞

    2016.9   医療薬学会  

    金光 祥臣

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Research Projects

  • トランスオミクス解析によるがん細胞の放射線耐性応答ネットワーク解明

    Grant number：22K07713

    2022.4 - 2025.3

    System name：科学研究費助成事業 基盤研究(C)

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    金光 祥臣

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

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  • Development of new therapeutic strategies to overcome cancer radioresistance; focusing on molecules that are increased in resistant cell lines

    Grant number：19K17258

    2019.4 - 2022.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Early-Career Scientists

    Awarding organization：Japan Society for the Promotion of Science

    KANEMITSU Yoshitomi

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    Radiotherapy is an essential component of cancer therapy. However, radioresistance remains a major obstacle to effective radiotherapy. The purpose of this study was to reveal new molecular mechanisms underlying radioresistance. To identify and quantification of novel radioresistance-related proteins, we conducted quantitative proteomic profiling on SAS and radioresistant cell lines (SAS-R). We found that protein disulfide isomerase (PDI) family proteins and peroxiredoxin 4 (Prx4) were significantly increased in SAS-R cells, as compared to SAS. Further, we also showed that knockdown of Prx4 in SAS-R cells leads to decreased radioresistance and resistance to H2O2.
    These results indicated that Prx4-PDI is one of the key molecules contributing to radioresistance in SAS-R cells. There is a possibility that specific suppression of Prx4 can be a novel approach to overcoming cancer radioresistance.

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  • Elucidation of the mechanism of radioresistance in cancer cells using trans-omics approach and development of clinical biomarkers for radiotherapy.

    Grant number：16K20909

    2016.4 - 2018.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Research category：Grant-in-Aid for Young Scientists (B)

    Awarding organization：Japan Society for the Promotion of Science

    Kanemitsu Yoshitomi, TOMIOKA Yoshihisa, MATSUMOTO Yotato, TSUKAMOTO Hiroki, FUKUMOTO Manabu, KUWAHARA Yoshikazu

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    In this study, we aimed to identify the molecules involved in radioresistance of cancer cells and to elucidate its mechanism. Here, we quantitatively compared the proteomes and the metabolomes of clinically relevant radioresistant (CRR) cell lines and their parent strains. In CRR cells, the chaperones and the proteins involved in oxidative stress were higher than control cell lines. Pathways such as amino acid metabolism and fatty acid metabolism were found to be highly enriched in CRR cells. These molecules can be expected as radiation tolerance markers and/or new targets for cancer therapies.

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