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Down-regulation of Irf8 by Lyz2-cre/loxP accelerates osteoclast differentiation in vitro

Emi Saito, Dai Suzuki, Daisuke Kurotaki, Ayako Mochizuki, Yoko Manome, Tetsuo Suzawa, Yoichi Toyoshima, Takahiro Ichikawa, Takahiro Funatsu, Tomio Inoue, Masamichi Takami, Tomohiko Tamura (+2 others)
2016 Cytotechnology (Dordrecht)  
Interferon regulatory factor 8 (Irf8) is a transcription factor that negatively regulates osteoclast differentiation and Irf8 global knockout (Irf8 -/-) mice have been shown to have reduced bone volume resulting from increased osteoclast numbers. However, detailed analysis of the functions of Irf8 in osteoclast precursors with a monocyte/macrophage linage is difficult, because the population and properties of hematopoietic cells in Irf8 -/mice are severely altered. Therefore, to clearly
more » ... e the functions of Irf8 during osteoclastogenesis, we established myeloid cell-specific Irf8 conditional knockout (Irf8 fl/fl ; Lyz2 cre/? ) mice. We found that trabecular bone volume in the Irf8 fl/fl ;Lyz2 cre/? mice was not significantly affected, while exposure to M-CSF and RANKL significantly increased TRAP activity in vitro in osteoclasts that underwent osteoclastogenesis from bone marrow-derived macrophages (BMMs) induced from bone marrow cells (BMCs) of those mice by addition of M-CSF. Our results also showed that expression of Irf8 mRNA and protein in BMMs obtained from Irf8 fl/fl ;Lyz2 cre/? mice and cultured with M-CSF was reduced. These findings predicted that Lyz2/Lyz2-cre expression is induced when BMCs differentiate into BMMs in cultures with M-CSF. In osteoclast differentiation cultures, Lyz2 was gradually increased by M-CSF during the first 3 days of culture, then rapidly decreased by the addition of RANKL with M-CSF during the next 3 days. Furthermore, BMCs differentiated into osteoclasts while maintaining a low Electronic supplementary material The online version of this article (level of Lyz2 expression when cultured simultaneously with both M-CSF and RANKL from the initiation of culture. These findings suggest that Lyz2-cre expression is induced along with differentiation to BMMs by BMCs obtained from Irf8 fl/fl ;Lyz2 cre/? mice and cultured with M-CSF. In addition, Irf8 was downregulated by activation of the cre/loxP recombination system in BMMs and osteoclastogenesis was accelerated. Based on our results, we propose the existence in vivo of a new lineage of osteoclast precursors among BMCs, which differentiate into osteoclasts without up-regulation of Lyz2 expression.
doi:10.1007/s10616-016-0013-z pmid:27502007 pmcid:PMC5461233 fatcat:wnpeerhrcnbednpjhfeakrx7be

Temporal evolution of ion fragment production from methylsilane by a hot tungsten wire

Satoru Yoshimura, Akinori Toh, Takahiro Toyoshima, Masato Kiuchi, Satoshi Hamaguchi
2006 Journal of Applied Physics  
doi:10.1063/1.2364050 fatcat:teooobkqavbbnmjrfjsfqz3gsu

A pilot-scale floating closed culture system for the multicellular cyanobacterium Arthrospira platensis NIES-39

Masakazu Toyoshima, Shimpei Aikawa, Takahiro Yamagishi, Akihiko Kondo, Hiroshi Kawai
2014 Journal of Applied Phycology  
Microalgae are considered to be efficient bioresources for biofuels and bio-based chemicals because they generally have high productivity. The filamentous cyanobacterium Arthrospira (Spirulina) platensis has been widely used for food, feed, and nutrient supplements and is usually cultivated in open ponds. In order to extend the surface area for growing this alga, we designed a pilot-scale floating closed culture system for cultivating A. platensis on open water and compared the growth and
more » ... y of the alga harvested at both subtropical and temperate regions. The biomass productivity of A. platensis NIES-39 was ca. 9 g dry biomass m −2 day −1 in summer at Awaji Island (warm temperature region) and ca. 10 and 6 g dry biomass m −2 day −1 in autumn and winter, respectively, at Ishigaki Island, (subtropical region) in Japan. If seawater can be used for culture media, culture cost can be reduced; therefore, we examined the influence of seawater salt concentrations on the growth of A. platensis NIES-39. Growth rates of A. platensis NIES-39 in diluted seawater with enrichment of 2.5 g L −1 NaNO3, 0.01 g L −1 FeSO 4 ·7H 2 O, and 0.08 g L −1 Na 2 EDTA were considerably lower than SOT medium, but the biomass productivity (dry weight) was comparable to SOT medium. This is explained by the heavier cell weight of the alga grown in modified seawater media compared to the alga grown in SOT medium. Furthermore, A. platensis grown in modified seawater-based medium exhibited self-flocculation and had more loosely coiled trichomes.
doi:10.1007/s10811-014-0484-2 pmid:26523091 pmcid:PMC4621703 fatcat:fo2z6xtqpbhu5hv7b6ej4xv2cq

Questionnaire survey on recruitment for Japanese Neurology Society
神経学会入会推進アンケートの解析結果

Kazutoshi Nishiyama, Takahiro Amano, Masashi Aoki, Takashi Inuzuka, Takayuki Taniwaki, Itaru Toyoshima, Yoichiro Hashimoto, Toshio Fukutake, Fumihito Yoshii, Yukio Ando
2016 Rinsho Shinkeigaku  
doi:10.5692/clinicalneurol.cn-000949 pmid:27890883 fatcat:zhwm42hcazbrbgecofusqsknli

Recognition of perception and the localization for aperture problem in visual pathway of brain

Isao Hayashi, Hisashi Toyoshima, Takahiro Yamanoi
2007 2007 IEEE International Conference on Systems, Man and Cybernetics  
The aperture problem is the one of the experiments to analyze binding mechanism of the space recognition with the human visual pathway. Nishina has already insisted that recognition of visual perception by the aperture problem depends in display time. In this paper, we discuss how other experimental parameters, e.g., radius, distance between circles, and speed of bar depend with recognition rate by measurement analysis of the perception. We simultaneously estimate the reaction latency of the
more » ... ception by electroencephalograms(EEG) analysis, and we localize the brain activity area by equivalent current dipole(ECD). We then discuss the relationship between the reaction latency of the visual evoked potential(VEP), event related potential(ERP) and the localized equivalent current dipole(ECD) in the visual pathway. By these discussion, we concluded that perception would be localized with the prefrontal lobe.
doi:10.1109/icsmc.2007.4413697 dblp:conf/smc/HayashiTY07 fatcat:ut3yfszoszenpj5aw5f5p7seiy

The actual state and problems in neurology training in medical schools
神経内科教育の実態と課題:医学部

Takayuki Taniwaki, Takashi Inuzuka, Fumihito Yoshii, Masashi Aoki, Takahiro Amano, Itaru Toyoshima, Toshio Fukutake, Yoichiro Hashimoto, Jun-ichi Kira
2014 Rinsho Shinkeigaku  
doi:10.5692/clinicalneurol.54.335 pmid:24807280 fatcat:m446qc7n6jc2bcxbt63247bzha

The actual state and problems in neurology training at hospital
神経内科教育の実態と課題:研修病院

Toshio Fukutake, Yoichiro Hashimoto, Takayuki Taniwaki, Itaru Toyoshima, Takahiro Amano, Masashi Aoki, Fumihito Yoshii, Takashi Inuzuka, Jun-ichi Kira
2014 Rinsho Shinkeigaku  
doi:10.5692/clinicalneurol.54.341 pmid:24807281 fatcat:z7ilap5dmvbhlmukowof36fdue

Synthesis of [211At]4-astato-L-phenylalanine by dihydroxyboryl-astatine substitution reaction in aqueous solution

Yoshifumi Shirakami, Tadashi Watabe, Honoka Obata, Kazuko Kaneda, Kazuhiro Ooe, Yuwei Liu, Takahiro Teramoto, Atsushi Toyoshima, Atsushi Shinohara, Eku Shimosegawa, Jun Hatazawa, Koichi Fukase
2021 Scientific Reports  
AbstractAstatine-211 (211At)-labeled phenylalanine is expected to be a promising agent for targeted alpha-particle therapy for the treatment of patients with glioma. The existing reactions to prepare the labeled compound usually require organic solvents and metals that are toxic and hazardous to the environment. In this study, we developed a novel method wherein astatination was realized via the substitution of 211At for a dihydroxyboryl group coupled to phenylalanine.
more » ... anine was obtained as the carrier-free product in aqueous medium in high radiochemical yields (98.1 ± 1.9%, n = 5). The crude reaction mixture was purified by solid-phase extraction, and the radiochemical purity of the product was 99.3 ± 0.7% (n = 5). The high yield and purity were attributed to the formation of [211At]AtI and AtI2− as the reactive intermediates in the astatination reaction. The reaction did not require any organic solvents or toxic reagents, suggesting that this method is suitable for clinical applications.
doi:10.1038/s41598-021-92476-6 pmid:34155314 fatcat:tan4icxyrbdc7l5rssfnn4ggli

The actual state and problems in neurology training at graduate school
神経内科教育の実態と課題:大学院

Jun-ichi Kira, Yasumasa Ohyagi, Takayuki Taniwaki, Takashi Inuzuka, Fumihito Yoshii, Masashi Aoki, Takahiro Amano, Itaru Toyoshima, Toshio Fukutake, Yoichiro Hashimoto
2014 Rinsho Shinkeigaku  
doi:10.5692/clinicalneurol.54.349 pmid:24807282 fatcat:jmupeeauavclhgmvhxegab7g5y

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

Tadashi Watabe, Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Yuwei Liu, Kazuhiro Ooe, Takahiro Teramoto, Atsushi Toyoshima, Eku Shimosegawa, Takashi Nakano, Yoshikatsu Kanai, Atsushi Shinohara, Jun Hatazawa
2020 OncoTarget  
Phenylalanine derivatives, which target tumors especially through L-type amino acid transporter-1 (LAT1), have elicited considerable attention. In this study, we evaluated the treatment effect of phenylalanine labeled with the alpha emitter astatine (211At-PA) in tumor bearing mice. The C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular 211At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor
more » ... 2,2,1)-heptane-2-carboxylic acid (BCH). BCH significantly inhibited para-211At-PA uptake in C6 glioma (12.2 ± 0.8%), U-87MG (27.6 ± 1.1%), and GL261 (12.6 ± 2.0%) cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters. Subsequently, xenograft and allograft models were prepared by subcutaneously injecting C6 glioma (n = 12) or GL-261 cells (n = 12), respectively. C6 glioma mice received three 211At-PA doses (0.1, 0.5, or 1 MBq, n = 3/dose), while GL261 mice received one high dose (1 MBq, n = 7). 211At-PA exhibited a tumor growth suppression effect in C6 glioma models in a dose-dependent manner as well as in GL-261 models. This phenylalanine derivative labeled with astatine may be applicable as an alpha therapy that specifically targets system L amino acid transporters.
doi:10.18632/oncotarget.27552 pmid:32341757 pmcid:PMC7170498 fatcat:iegspnvezbfvpd2mty3kzjmzbm

Prevalence of serrated polyposis syndrome and its association with synchronous advanced adenoma and lifestyle

NAOYA TOYOSHIMA, TAKU SAKAMOTO, MAKOMO MAKAZU, TAKESHI NAKAJIMA, TAKAHISA MATSUDA, RYOJI KUSHIMA, TADAKAZU SHIMODA, TAKAHIRO FUJII, HARUHIRO INOUE, SHIN-EI KUDO, YUTAKA SAITO
2014 Molecular and clinical oncology  
We assessed the clinicopathological characteristics of patients with serrated polyposis syndrome (SPS) and the incidence of advanced adenoma/colorectal cancer (CRC). We prospectively enrolled 249 consecutive patients who underwent colonoscopy at the National Cancer Center Hospital over a 6-month period. All the polyps were diagnosed using magnification colonoscopy and resection/biopsy. The enrolled patients were divided into two groups, i) those with ≥5 histologically diagnosed hyperplastic
more » ... ps (HPs) proximal to the sigmoid colon, with at least 2 polyps >10 mm in diameter and ii) those with ≥20 HPs distributed throughout the colon. The clinical characteristics of the two groups were compared, including lifestyle, family history of CRC and colonoscopic findings. HPs were identified in 228 patients, of whom 21 (8.4%) had SPS. All 21 patients had ≥20 HPs distributed throughout the colon, with none having >2 HPs ≥1 cm in diameter in the right colon. Synchronous advanced adenoma/CRC was diagnosed in 76̸249 (30.5%) patients. The prevalence of advanced adenoma/CRC was higher among patients with compared to those without SPS (P=0.075). SPS was also associated with older age and higher body mass index (BMI). Our results suggested that older age and higher BMI are independent risk factors for SPS. Advanced adenoma/CRC tended to occur more frequently among patients with compared to those without SPS, although the difference was not statistically significant.
doi:10.3892/mco.2014.423 pmid:25469272 pmcid:PMC4251102 fatcat:3uugpci7qnerlis2tjl7z4ts2a

Association of cytokeratin 17 expression with differentiation in oral squamous cell carcinoma

Ryoji Kitamura, Takeshi Toyoshima, Hideaki Tanaka, Shintaro Kawano, Takahiro Kiyosue, Ryota Matsubara, Yuichi Goto, Mitsuhiro Hirano, Kazunari Oobu, Seiji Nakamura
2012 Journal of Cancer Research and Clinical Oncology  
Moreover, CK17 mRNA is sig-niWcantly over-expressed compared to CK19 mRNA and CK20 mRNA in OSCC (Toyoshima et al. 2009 ).  ...  based on the microarray and the real-time RT-PCR analyses have reported that the sig-niWcant up-regulation and the strong over-expression of CK17 could exhibit the utility as diagnostic marker of OSCC (Toyoshima  ... 
doi:10.1007/s00432-012-1202-6 pmid:22466643 pmcid:PMC3397222 fatcat:zywv7tqyajeb5hakdmzoq2kqse

Challenges for Better Diagnosis and Management of Pancreatic and Biliary Tract Cancers Focusing on Blood Biomarkers: A Systematic Review

Hiroto Tominaga, Juntaro Matsuzaki, Chihiro Oikawa, Kensho Toyoshima, Haruki Manabe, Eriko Ozawa, Atsushi Shimamura, Riko Yokoyama, Yusuke Serizawa, Takahiro Ochiya, Yoshimasa Saito
2021 Cancers  
pancreatic cancer (PCa) and biliary tract cancer (BTC) are cancers with a poor prognosis and few effective treatments. One of the reasons for this is late detection. Many researchers are tackling to develop non-invasive biomarkers for cancer, but few are specific for PCa or BTC. In addition, genetic abnormalities occur in cancer tissues, which ultimately affect the expression of various molecules. Therefore, it is important to identify molecules that are altered in PCa and BTC. For this
more » ... ic review, a systematic review of Medline and Embase to select biomarker studies of PCa and BTC patients was conducted. Results: after reviewing 72 studies, 79 biomarker candidates were identified, including 22 nucleic acids, 43 proteins, and 14 immune cell types. Of the 72 studies, 61 examined PCa, and 11 examined BTC. Conclusion: PCa and BTC are characterized by nucleic acid, protein, and immune cell profiles that are markedly different from those of healthy subjects. These altered molecules and cell subsets may serve as cancer-specific biomarkers, particularly in blood. Further studies are needed to better understand the diagnosis and prognosis of PCa and BTC.
doi:10.3390/cancers13164220 fatcat:jc63owf63bbfzkkywkkugazz24

Risk of Gastrointestinal Perforation in Patients with Metastatic Colorectal Cancer Receiving Bevacizumab
切除不能進行再発大腸癌に対するBevacizumab併用化学療法における消化管穿孔危険因子の検討

Ryuji Akai, Takeshi Endo, Akira Toyoshima, Takahiro Amano
2016 The Japanese Journal of Gastroenterological Surgery  
切除不能進行再発大腸癌に対する Bevacizumab 併用化学療法における 消化管穿孔危険因子の検討 赤井 隆司 1) 遠藤 健 1) 豊島 明 1) 天野 隆晧 1) 1) 日本赤十字社医療センター大腸肛門外科 目的:Bevacizumab 併用化学療法を行った切除不能進行再発大腸癌症例を対象に,消化管穿孔の危険因 子を検討する.方法:2007 年 7 月から 2012 年 12 月までに当院で Bevacizumab 併用化学療法を開始した切 除不能進行再発大腸癌症例 195 例をレトロスペクティブに解析した.消化管穿孔の危険因子を単変量,多 変量ロジスティック回帰分析により検索した.結果:消化管穿孔は 7 例(3.6%)に認めた.単変量解析で は,直腸癌(オッズ比 4.933,95%信頼区間 1.061~22.947) ,放射線照射既往(オッズ比 39.120,95%信頼 区間 4.518~338.691)の二つの因子が統計学的有意(P<0.05)に消化管穿孔の発生と関連していた.多変 量解析では,放射線照射既往のみが独立して有意な因子であり,照射既往ありの調整オッズ比は
more » ... .831 (95%信頼区間 3.566~340.204)であった.結語:放射線照射症例に対する Bevacizumab 投与は慎重に行わ れるべきであると考えられた. キーワード:切除不能進行再発大腸癌,化学療法,Bevacizumab,消化管穿孔,放射線照射 はじめに Bevacizumab は血管内皮細胞増殖因子(vascular endothelial growth factor;以下,VEGF と略記)に対する 遺伝子組換え IgG1 ヒト化モノクローナル抗体であり,血中 VEGF と特異的に結合し,血管内皮細胞の VEGFR への結合を阻害することにより血管新生を抑制する 1 ) .また,腫瘍血管の構造や機能を正常化し, 腫瘍組織周辺の間質圧を減少させることにより,抗癌剤の組織移行性を高めるとされる 2 )~ 4 ) .したがって, 他の抗癌剤と併用することで抗腫瘍効果が期待される薬剤であり,切除不能進行再発大腸癌に適応を有す る本邦初の分子標的薬として,2007 年 6 月より臨床使用が開始され,現在では広く用いられている.当院 においても 2012 年 12 月末で 195 例に達し,今後もますます増加することが予想される.Bevacizumab の 副作用として消化管穿孔があげられるが,頻度は低いものの重篤化することも多く注意すべき有害事象で ある. 目 的 切除不能進行再発大腸癌に対する Bevacizumab 併用化学療法における消化管穿孔の危険因子を検討する. 方 法 2007 年 7 月から 2012 年 12 月までに当院で Bevacizumab 併用化学療法を開始した切除不能進行再発大腸 〈2015 年 10 月 27 日受理〉別刷請求先:赤井 隆司 〒 150-8935 渋谷区広尾 4-1-22 日本赤十字社医療センター大腸肛門外科 日本消化器外科学会雑誌.2016;49(2):75-83 Purpose: To examine the risk factors of gastrointestinal perforation in patients with metastatic colorectal cancer receiving Bevacizumab. Methods: We treated 195 cases of metastatic colorectal cancer with Bevacizumab from July 2007 to December 2012. We examined the risk factors of the gastrointestinal perforation by univariate and multivariate analysis. Results: Seven (3.6%) patients of those cases had gastrointestinal perforation. According to univariate analysis, two factors, rectal cancer and previous radiation exposure, were statistically significant. In this analysis, the odds ratio of rectal cancer is 4.933 (95% CI: 1.061-22.947) and the odds ratio of radiation exposure was 39.120 (95% CI: 4.518-338.691). Furthermore, only past radiation exposure was an independent statistically significant factor in multivariate analysis. At this time, the adjustment odds ratio with past radiation exposure was 34.831 (95% CI: 3.566-340.204). Conclusions: Bevacizumab dosage for radiation exposure cases should be provided carefully.
doi:10.5833/jjgs.2014.0171 fatcat:f7uew7jc2bfoznh3gccrjtdkd4

Treatment of tumor thrombus in the superior mesenteric vein due to advanced colon cancer with complete surgical resection and chemotherapy: a case report

Yoshitsugu Yanagida, Takahiro Amano, Ryuji Akai, Akira Toyoshima, Jotaro Kobayashi, Takuya Hashimoto, Eiji Sunami, Toshio Kumasaka, Shin Sasaki
2020 Surgical Case Reports  
Background Tumor thrombus in the superior mesenteric vein secondary to colon cancer is rare. We report a case of tumor thrombus in the superior mesenteric vein and liver metastasis due to advanced colon cancer that was treated with chemotherapy and complete surgical resection. Case presentation A 72-year-old man after transverse colectomy with lymph node dissection for advanced colon cancer was diagnosed with tumor thrombus in the superior mesenteric vein and liver metastasis. He underwent
more » ... ant chemotherapy and had complete surgical tumor resection involving tumor thrombectomy and hepatectomy. There has been no recurrence at 36 months after surgery. Conclusion Herein, we report a rare case of tumor thrombus in the superior mesenteric vein related to advanced colon cancer. The combination of chemotherapy and complete surgical tumor resection may provide long-term survival.
doi:10.1186/s40792-020-01091-6 pmid:33315157 fatcat:qfeg7ovddjdifaphnanpb4ylhq
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