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Mori, Tadashi, Gaku Fukuhara e Takehiko Wada. "Yoshihisa Inoue—A researcher’s quest for photochirogenesis". Journal of Photochemistry and Photobiology A: Chemistry 331 (dezembro de 2016): 2–7. http://dx.doi.org/10.1016/j.jphotochem.2016.08.006.
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Funato, Yosuke, Kazuharu Furutani, Yoshihisa Kurachi e Hiroaki Miki. "Rebuttal from Yosuke Funato, Kazuharu Furutani, Yoshihisa Kurachi and Hiroaki Miki". Journal of Physiology 596, n.º 5 (31 de janeiro de 2018): 751. http://dx.doi.org/10.1113/jp275706.
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Hui-Mei, Chen. "Les sources d’inspiration et les influences dans la musique de Yoshihisa Taira". Cipango, n.º 15 (1 de janeiro de 2008): 294–97. http://dx.doi.org/10.4000/cipango.449.
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Credi, Alberto. "Supramolecular Photochemistry. Controlling Photochemical Processes. Herausgegeben von V. Ramamurthy und Yoshihisa Inoue." Angewandte Chemie 124, n.º 26 (15 de junho de 2012): 6417–18. http://dx.doi.org/10.1002/ange.201202588.
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Credi, Alberto. "Supramolecular Photochemistry. Controlling Photochemical Processes. Edited by V. Ramamurthy and Yoshihisa Inoue." Angewandte Chemie International Edition 51, n.º 26 (15 de junho de 2012): 6311–12. http://dx.doi.org/10.1002/anie.201202588.
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Morooka, Hiroyo. "méditation comme moyen de synthèse culturelle dans les œuvres du compositeur Yoshihisa Yaïra". ALTERNATIVE FRANCOPHONE 2, n.º 9 (13 de abril de 2021): 72–85. http://dx.doi.org/10.29173/af29425.
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Le compositeur Yoshihisa Taïra (1937-2005) cherche – dans sa composition – à réaliser une synthèse culturelle entre la France, où il s’est formé et a vécu, et le Japon, son pays d'origine. Il utilise alors la méditation comme thème musical pour se libérer de l’intellectualisation et de la verbalisation de la musique, et ce, dans le but de revenir à l’écoute en tant qu’essence musicale. En utilisant le concept du ma (vide), en s’inspirant de la pensée bouddhiste zen, Taïra réussit à trouver une position équilibrée avec le contexte esthétique de la postmodernité française représentée par Jean-François Lyotard.
Cet article creuse donc ce en quoi la méditation est la synthèse culturelle pour Taïra, en analysant du point de vue musical et philosophique, la possibilité de l’existence d’un croisement idéologique entre ces deux cultures qui inciterait le compositeur à retourner vers l’inspiration de la culture japonaise, à l’aide de la pensée issue de Logique du lieu de Kitarô Nishida.
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TAMURA, SAYA, TOMOKO FUKUDA, ELENA A. PIMENOVA, EKATERINA A. PETRUNENKO, PAVEL V. KRESTOV, SVETLANA N. BONDARCHUK, OLGA A. CHERNYAGINA et al. "Molecular and cytological evidences denied the immediate-hybrid hypothesis for Saxifraga yuparensis (sect. Bronchiales, Saxifragaceae) endemic to Mt. Yubari in Hokkaido, northern Japan". Phytotaxa 373, n.º 1 (23 de outubro de 2018): 53. http://dx.doi.org/10.11646/phytotaxa.373.1.2.
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SAYA TAMURA, TOMOKO FUKUDA, ELENA A. PIMENOVA, EKATERINA A. PETRUNENKO, PAVEL V. KRESTOV, SVETLANA N. BONDARCHUK, OLGA A. CHERNYAGINA, YOSHIHISA SUYAMA, YOSHIHIRO TSUNAMOTO, AYUMU MATSUO, HAYATO TSUBOI, HIDEKI TAKAHASHI, KEN SATO, YOKO NISHIKAWA, TAKASHI SHIMAMURA, HIROKO FUJITA & KOH NAKAMURA An alpine plant Saxifraga yuparensis is endemic to a scree consisting of greenschist of Mt. Yubari in Hokkaido, Japan and it has been proposed as an immediate hybrid derived from two species of the same section Bronchiales based on morphological intermediacy: namely S. nishidae, a diploid species endemic to a nearby cliff composed of greenschist and tetraploid S. rebunshirensis comparatively broadly distributed in Japan and Russian Far East. Saxifraga yuparensis is red-listed and it is crucial for conservation planning to clarify whether this is an immediate hybrid and lacks a unique gene pool. The immediate-hybrid hypothesis was tested by molecular and cytological data. In nuclear ribosomal and chloroplast DNA trees based on maximum parsimony and Bayesian criteria, S. yuparensis and S. rebunshirensis formed a clade with several other congeners while S. nishidae formed another distinct clade. Genome-wide SNP data clearly separated these three species in principal coordinate space, placing S. yuparensis not in-between of S. rebunshirensis and S. nishidae. Chromosome observation indicated that S. yuparensis is tetraploid, not triploid directly derived from diploid-tetraploid crossing. Additionally, observation of herbarium specimens revealed that leaf apex shape of S. yuparensis fell within the variation of S. rebunshirensis. These results indicate that S. yuparensis is not an immediate hybrid of S. rebunshirensis and S. nishidae but a distinct lineage and an extremely narrow endemic species, that deserves for intensive conservation.
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Rivera, Matthew. "Political Order and Forms of Communication in Medieval and Early Modern Europe ed. by Yoshihisa Hattor". Comitatus: A Journal of Medieval and Renaissance Studies 46, n.º 1 (2015): 284–87. http://dx.doi.org/10.1353/cjm.2015.0048.
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von Zelewsky, Axel. "Chiral Photochemistry. (Series: Molecular and Supramolecular Photochemistry, Vol. 11.). Edited by Yoshihisa Inoue and Vaidhyanathan Ramamurthy." Angewandte Chemie International Edition 44, n.º 23 (6 de junho de 2005): 3515–16. http://dx.doi.org/10.1002/anie.200485261.
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Mori, Tadashi, Gaku Fukuhara e Takehiko Wada. "The themed issue in honor of Prof. Yoshihisa Inoue for his contribution on molecular and supramolecular photochemistry". Journal of Photochemistry and Photobiology A: Chemistry 331 (dezembro de 2016): 1. http://dx.doi.org/10.1016/j.jphotochem.2016.09.029.
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von Zelewsky, Alexander. "Chiral Photochemistry. Band 11 der Reihe “Molecular and Supramolecular Photochemistry”. Herausgegeben von Yoshihisa Inoue und Vaidhyanathan Ramamurthy." Angewandte Chemie 117, n.º 23 (6 de junho de 2005): 3582. http://dx.doi.org/10.1002/ange.200485261.
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Reynolds, E. Bruce. "The Making of Japanese Manchuria, 1904–1932. By Yoshihisa Tak Matsusaka. Cambridge: Harvard University Asia Center, 2001. xviii, 522 pp. $49.50 (cloth)." Journal of Asian Studies 61, n.º 2 (maio de 2002): 726–27. http://dx.doi.org/10.2307/2700338.
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Guelcher, G. "The Making of Japanese Manchuria, 1904-1932, by Yoshihisa Tak Matsusaka. Cambridge: Harvard University Asia Center, 2001, 522 pp. $52.00 (hardcover ISBN 0-674-00369-1)". Social Science Japan Journal 7, n.º 1 (1 de abril de 2004): 132–34. http://dx.doi.org/10.1093/ssjj/7.1.132.
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Oka, T., e A. Nakano. "Inhibition of GTP hydrolysis by Sar1p causes accumulation of vesicles that are a functional intermediate of the ER-to-Golgi transport in yeast". Journal of Cell Biology 124, n.º 4 (15 de fevereiro de 1994): 425–34. http://dx.doi.org/10.1083/jcb.124.4.425.
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The SAR1 gene product (Sar1p), a 21-kD GTPase, is a key component of the ER-to-Golgi transport in the budding yeast. We previously reported that the in vitro reconstitution of protein transport from the ER to the Golgi was dependent on Sar1p and Sec12p (Oka, T., S. Nishikawa, and A. Nakano. 1991. J. Cell Biol. 114:671-679). Sec12p is an integral membrane protein in the ER and is essential for the Sar1 function. In this paper, we show that Sar1p can remedy the temperature-sensitive defect of the sec12 mutant membranes, which is in the formation of ER-to-Golgi transport vesicles. The addition of Sar1p promotes vesicle formation from the ER irrespective of the GTP- or GTP gamma S-bound form, indicating that the active form of Sar1p but not the hydrolysis of GTP is required for this process. The inhibition of GTP hydrolysis blocks transport of vesicles to the Golgi and thus causes their accumulation. The accumulating vesicles, which carry Sar1p on them, can be separated from other membranes, and, after an appropriate wash that removes Sar1p, are capable of delivering the content to the Golgi when added back to fresh membranes. Thus we have established a new method for isolation of functional intermediate vesicles in the ER-to-Golgi transport. The sec23 mutant is defective in activation of Sar1 GTPase (Yoshihisa, T., C. Barlowe, and R. Schekman. 1993. Science (Wash. DC). 259:1466-1468). The membranes and cytosol from the sec23 mutant show only a partial defect in vesicle formation and this defect is also suppressed by the increase of Sar1p. Again GTP hydrolysis is not needed for the suppression of the defect in vesicle formation. Based on these results, we propose a model in which Sar1p in the GTP-bound form is required for the formation of transport vesicles from the ER and the GTP hydrolysis by Sar1p is essential for entering the next step of vesicular transport to the Golgi apparatus.
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Shimizu, Chikako, Yoshihisa Wakita, Youichi Tsuchiya e Toshitaka Nabeshima. "Erratum: Chikako, S.; Yoshihisa, W.; Youichi, T.; Toshitaka, N. Influence of Housing Systems on Physical, Emotional, and Cognitive Functions with Aging in DBA/2CrSlc Mice Animals 2020, 10, 746". Animals 10, n.º 5 (7 de maio de 2020): 813. http://dx.doi.org/10.3390/ani10050813.
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Turro, Nicholas J. "Chiral Photochemistry. Molecular and Supramolecular Photochemistry, Volume 11 Edited by Yoshihisa Inoue (Osaka University) and Vaidhyanathan Ramamurthy (Tulane University). Marcel Dekker: New York. 2004. xii + 686 pp. $185.00. ISBN 0-8247-5710-6." Journal of the American Chemical Society 127, n.º 14 (abril de 2005): 5272. http://dx.doi.org/10.1021/ja0409917.
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Suzuki, Nobuo. "Uchida Yoshihiko:". History of Economic Thought 55, n.º 1 (2013): 1–17. http://dx.doi.org/10.5362/jshet.55.1_1.
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Shaimardanova, Nazigul. "TRANSFORMATION OF JAPANESE FOREIGN POLICY IN THE XXI CENTURY – RESPONSE TO THE CHANGES IN THE ARCHITECTURE OF GLOBAL AND REGIONAL RELATIONS". KAZAKHSTAN ORIENTAL STUDIES 5, n.º 1 (11 de junho de 2024): 83–94. http://dx.doi.org/10.63051/kos.2023.1.83.
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The article analyzes the political concepts of Japanese prime ministers, starting with the pro-American policy of Junichiro Koizumi, whose actions contributed to Japan's participation in anti-terrorist operations in Afghanistan and Iraq, and also led to complications in relations with China and South Korea. Shinzo Abe strengthened the Japan-US alliance and placed great emphasis on Asian strategic diplomacy; Yasuo Fukuda paid special attention to integration in the Pacific region; Taro Aso conducted value-oriented diplomacy; Yukio Hatoyama proposed the idea of "fraternal political philosophy" based on cooperation and multipolarity; Naoto Kan and Yoshihiko Noda continued the policy of strengthening the alliance with the US and balancing relations with regional actors. Shinzo Abe's second term was marked by Japan's aspiration to revive as a leading world power and a review of the pacifist articles of the constitution. The national security strategy of Suga Yoshihide was characterized by strengthening ties with the US and a focus on environmental issues. The current Prime Minister, Kishida Fumio, continues this line, however, he faces new challenges such as the Covid-19 pandemic and tectonic shifts in global geopolitics. Despite changes in political concepts, Japan's foreign policy maintains stability, especially in terms of the alliance with the US, relations with China, and attention to Central Asia and Kazakhstan. Japan remains an important and stable partner for the countries of Central Asia, striving to strengthen trade and economic ties and responding to new global and regional challenges.
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Futamura, Manabu, Hirotoshi Iihara, Hiroko Bando, Yoshihiro Kawaguchi, Yutaka Mizuno, Akari Murakami, Masaaki Kawai et al. "Abstract PO1-12-09: Doublet or triplet antiemetic prophylaxis for trastuzumab deruxtecan-induced nausea and vomiting: An open-label, randomized, multicenter, exploratory phase 2 study". Cancer Research 84, n.º 9_Supplement (2 de maio de 2024): PO1–12–09—PO1–12–09. http://dx.doi.org/10.1158/1538-7445.sabcs23-po1-12-09.
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Abstract Background: Trastuzumab deruxtecan (T-DXd) is classified as an anticancer agent that poses a moderate emetic risk according to international guidelines for antiemetic therapy, which recommend emesis prophylaxis using a two-drug combination therapy comprising 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). The incidence rates of nausea and vomiting in patients in DESTINY BREAST01 and DESTINY BREAST03 were 77.7%, 45.7%, 72.8%, and 44%, respectively. However, no effective antiemetic therapy was observed. The high nausea and vomiting incidence associated with T-DXd is problematic. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment with 5-HT3RA and DEX, with or without a neurokinin-1 receptor antagonist (NK1RA), in preventing T-DXd-induced nausea and vomiting. Methods: We conducted an open-label, randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer scheduled to receive T-DXd were enrolled in this study. Patients were randomly assigned to receive granisetron and dexamethasone (arm GD) or granisetron, dexamethasone, and aprepitant (fosaprepitant; arm GDA). Patients in both treatment arms were administered granisetron (1 mg i.v. 30 min before T-DXd on day 1). Those in the GD arm were administered DEX (6.6 mg i.v. 30 min before T-DXd on day 1 and 8 mg p.o. on days 2–3). The patients in the GDA arm were administered DEX (9.9 mg i.v. 30 min before T-DXd on day 1) and NK1-RA (125 mg of aprepitant p.o. 60 min before chemotherapy on day 1 and 80 mg p.o. on days 2 and 3, or 150 mg fosaprepitant i.v. 60 min before T-DXd on day 1). The primary endpoint was complete response (CR; no emesis or rescue therapy) during the overall phase (0–120 h after the start of T-DXd). The primary endpoint was estimated using the CR rate and 95% confidence intervals (CIs) following the Pearson–Clopper method. The Cochran–Mantel–Haenszel test was used to compare the exploratory results between the two treatment arms with age strata and previous experience with chemotherapy-induced nausea and vomiting. Logistic regression analyses were performed to determine the risk factors associated with the non-achievement of CR, non-achievement of complete control (CC), and non-achievement of total control (TC) in the overall and long-overall phases. Results: Between September 2020 and March 2023, 40 patients were enrolled and randomly assigned to either the GD (n = 19) or GDA (n = 21) arm. In the GDA group, one patient who did not complete the rescue medication listed in the diary was excluded from the efficacy analysis, including rescue medication use. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA groups, respectively (odds ratio [OR], 0.1334; 95% confidence interval [CI], 0.0232–0.7672; P = 0.0190), with a difference of 33.2%. The CR rates during the long-overall phase were 31.6% in the GD arm and 70.0% in the GDA arm (OR, 0.1073; 95% CI, 0.0185–0.6239; P = 0.0087), a difference of 38.4%. NK1RA use was associated with a significant decrease in the non-achievement of CR, CC, and TC in the overall and long-overall phases. Only patients in the GDA arm (33.3%) reported being “very satisfied” with the treatment. No grade 3 or 4 toxicities related to antiemetic therapy were observed. Conclusions: Breast cancer patients receiving T-DXd require triple therapy, including mandatory NK1RA administration, for antiemetic prophylaxis. Further investigation is needed to explore the development of more appropriate combination therapies for T-DXd-induced nausea and vomiting. Citation Format: Manabu Futamura, Hirotoshi Iihara, Hiroko Bando, Yoshihiro Kawaguchi, Yutaka Mizuno, Akari Murakami, Masaaki Kawai, Tomokazu Iyoda, Kazshige Ishida, Kazuhiro Ishihara, Takumi Nakada, Makoto Takeuchi, Mika Kitahora, Yoshihisa Tokumaru, Mototsugu Shimokawa, Nobuhisa Matsuhashi. Doublet or triplet antiemetic prophylaxis for trastuzumab deruxtecan-induced nausea and vomiting: An open-label, randomized, multicenter, exploratory phase 2 study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-09.
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Gopalakrishnan, Murali. "Potassium Ion Channels: Molecular Structure, Function and Diseases Edited by Yoshihisa Kurachi, Lily Yeh Jan, and Michel Lazdunzki. Academic Press, San Diego, CA. 1999. xxiv + 492 pp. 15 × 22 cm. ISBN 0-12-153346-8. $99.95." Journal of Medicinal Chemistry 43, n.º 11 (junho de 2000): 2291–92. http://dx.doi.org/10.1021/jm000166a.
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Mandavilli, Apoorva. "Profile: Yoshihiro Kawaoka". Nature Medicine 12, n.º 5 (27 de abril de 2006): 489. http://dx.doi.org/10.1038/nm0506-489.
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Ouchi, Mieko. "Translating Alberta". Canadian Theatre Review 136 (setembro de 2008): 50–53. http://dx.doi.org/10.3138/ctr.136.010.
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I first met the remarkable Toyoshi (Yoshi) Yoshihara in Calgary in 2003, as my first play The Red Priest (Eight Ways to Say Goodbye) was debuting at Alberta Theatre Project's playRites Festival. Born and raised in Tokyo, Yoshihara formally studied Russian language and literature at Waseda University while informally getting involved in theatre after hours in a student club. After a successful career in business, Yoshihara returned to his first love, theatre, and has become Japan's foremost translator of Canadian work. He has translated an astonishing list of Canuck playwrights, from Anne Chislett to Daniel McIvor. Even more interestingly, he has translated the plays of many Albertan playwrights, including John Murrell, Sharon Pollock, Frank Moher and, in recent years, myself. Yoshihara received an honorary doctorate (D. Litt.) from McMaster University in recognition of his introducing Canadian theatre to Japan, and last year, the Playwrights Guild of Canada honoured him with a lifetime membership to recognize his contribution to Canadian playwriting. I spoke with Yoshi from the Banff playRites Colony about his work as a translator and his long-standing connections with Alberta.
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Oshi, Masanori, Joy Sarkar, Rongrong Wu, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Itaru Endo e Kazuaki Takabe. "Abstract 6112: Clinical relevance of intra-tumoral density of regulatory T cells as a predictive factor for chemotherapy response in metastatic colorectal cancer". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 6112. http://dx.doi.org/10.1158/1538-7445.am2022-6112.
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Abstract Background: Within the tumor microenvironment, regulatory T cells (Tregs) are potent facilitators of immune tolerance, and in most solid tumors a higher proportion of Tregs compared to cytotoxic T cells predicts a worse outcome. However, the role of Tregs in colorectal cancer (CRC) is more controversial, possibly due in part to the effect of the gut microbiome on colorectal tumors. We explore the association between colorectal cancer (CRC) Treg density, cancer biology, and clinical outcome. The aim of the study is to investigate the clinical relevance of the fraction of Tregs within the colorectal cancer TME using xCell score with mRNA expression data across several CRC cohorts. Methods: We used xCell to estimate intra-tumoral Tregs in 898 CRC patients in the Cancer Genome Atlas (TCGA) and GCE39582 cohorts. into two groups based on high versus low proportions of Tregs. We studied the correlation between intra-tumoral Treg density and cancer biology including host immune response, ICM expression, and the tumor microbiome by comparing gene ex-pression between the two groups. We further examined two CRC cohorts which contained data on response to neoadjuvant chemotherapy using mFOLFOX6 and bevacizumab, in order to explore the association between Treg infiltration and response to treatment. Results: High-Treg CRCs enriched immune response-related gene sets; inflammatory response, IFN-γ and IFN-α response, IL2/IL6 signaling, and allograft rejection, and had significantly high infiltration of CD8, CD4, M1/M2 macrophage, and dendritic cells in both cohorts. While high-Treg CRCs enriched multiple pro-cancer signaling pathways compared to low-Treg CRCs, such as Epithelial Mesenchymal Transition, K-ras, Hypoxia, TGF-β, TNF-α, and angiogenesis, Treg infiltration was surprisingly associated with earlier CRC stage in TCGA. Metastatic CRCs with more Tregs showed a significantly better response to mFOLFOX6 versus low-Treg CRC metastases (88.9% response vs. 16.7%, p < 0.001). Finally, high-Treg CRCs were associated with increased expression of immune check-point molecules PD-L1/PD-L2, CTLA4, TIGIT and BTLA, implying susceptibility to immunotherapy. Conclusion: We show that unlike in other cancers, Tregs in CRC are not necessarily a marker of poor prognosis. High-Treg CRC enriched not only cancer aggravating gene sets, such as EMT, KRAS, TGF-β and angiogenesis, but also immune response-related gene sets, which is consistent with high infiltration of anti-cancerous immune cells. High Treg density was a predictor of response to chemotherapy in metastatic CRC. Citation Format: Masanori Oshi, Joy Sarkar, Rongrong Wu, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe. Clinical relevance of intra-tumoral density of regulatory T cells as a predictive factor for chemotherapy response in metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6112.
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Oshi, Masanori, Yoshihisa Tokumaru, Nobuhiko Sugito, Mahato Sasamoto, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo e Kazuaki Takabe. "Abstract P3-05-33: High expression of MiR-99b in breast cancer is associated with cell proliferation signaling and worse patient survivals in breast cancer". Cancer Research 83, n.º 5_Supplement (1 de março de 2023): P3–05–33—P3–05–33. http://dx.doi.org/10.1158/1538-7445.sabcs22-p3-05-33.
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Abstract Background: MicroRNA (miR) is single stranded RNA which regulates the gene expression epigenetically by inhibiting the mRNA translation as well as promoting mRNA degradation. MiR-99b is known as a regulator of mechanistic target of rapamycin (mTOR) signaling and was reported as both onco-miR that promote cell proliferation and tumor suppressor-miR in multiple cancers. We hypothesized that there is a complex interaction between miR-99b and cancer signaling pathways as well as tumor microenvironment, which may influence outcomes. Methods: We studied the clinical relevance of miR-99b expression by performing in silico analyses of 1,961 breast cancer patients using two independent large cohorts; METABRIC and TCGA. Results: We found that high miR-99b breast cancer enriched MTORC1 signaling gene set (normalized enrichment score (NES)>1.50 in both cohorts), but not epithelial mesenchymal transition, NF-kB, nor TGF-β signaling gene sets (all false discovery rate (FDR)>0.40). High miR-99b breast cancer was significantly associated with high rates of mutation scores; silent- and non-silent-mutation rate, fraction altered, single-nucleotide variant neoantigens, as well as intratumor heterogeneity and homologous recombination defects. MiR-99b high tumors also enriched several cell proliferation-related gene sets; E2F targets, G2M checkpoint, and Mitotic spindle signaling, and was significantly associated with pathological grade, but not with subtype nor AJCC stage. High miR-99b breast cancer was significantly associated with low fraction of several stromal cells, including adipocytes cells, keratinocytes cells, and lymphatic endothelial cells in tumor microenvironment (all p< 0.001). On the other hand, miR-99b expression was not associated with immune function nor immune cell infiltration in breast cancer, except for dendritic cells (p=0.006 and 0.020, respectively). Finally, breast cancer with high miR-99b expression was significantly associated with worse overall survival (OS) (hazard ratio (HR)=1.23 (p< 0.001) and 1.26 (p=0.027), respectively) and disease-specific survival (DSS) (HR=1.28 (p< 0.001) and 1.39 (p=0.022), respectively), particularly DSS for ER-positive/HER2-negative breast cancer (HR=1.29 (p< 0.001) and 1.82 (p=0.017), respectively), consistently in two cohorts. In conclusion, we found that high miR-99b expressing breast cancer was significantly associated with not only MTORC1 but also cell proliferation and worse patient outcomes particularly in ER-positive/HER2-negative breast cancer. Citation Format: Masanori Oshi, Yoshihisa Tokumaru, Nobuhiko Sugito, Mahato Sasamoto, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. High expression of MiR-99b in breast cancer is associated with cell proliferation signaling and worse patient survivals in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-33.
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Tada, Isao, e Yoshiki Aoki. "Obituary: Dr. Yoshihito Otsuji". Parasitology International 64, n.º 5 (outubro de 2015): 478. http://dx.doi.org/10.1016/j.parint.2015.05.010.
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Murakami, Masahiro. "Yoshihiko Ito (1937–2006)". Angewandte Chemie International Edition 46, n.º 18 (27 de abril de 2007): 3176. http://dx.doi.org/10.1002/anie.200701275.
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Murakami, Masahiro. "Yoshihiko Ito (1937–2006)". Angewandte Chemie 119, n.º 18 (27 de abril de 2007): 3238. http://dx.doi.org/10.1002/ange.200701275.
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Yoshihara, Kumiko, Adriana Bona Matos e Marcelo Giannini. "Entrevista com Kumiko Yoshihara". Journal of Clinical Dentistry and Research 20, n.º 2 (30 de agosto de 2023): 8–11. http://dx.doi.org/10.14436/2447-911x.20.2.008-011.int.
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Bacharelado em Odontologia (DDS) pela Faculdade de Odontologia da Universidade de Okayama, Japão. Residente Clínica no Centro de Treinamento Clínico de Pós-Graduados, Universidade de Okayama, Japão. Estudante de Doutorado no Departamento de Reabilitação Funcional Oclusal e Oral, Escola de Pós-graduação em Medicina, Odontologia e Ciências Farmacêuticas, Universidade de Okayama, Japão. Estudante de Doutorado no laboratório BIOMAT, Departamento de Ciências da Saúde Oral, Universidade de Leuven, Bélgica. Professora Assistente do Centro de Inovações em Medicina Clínica, Universidade de Okayama, Japão. Pesquisadora Sênior do Instituto de Pesquisa em Saúde, Instituto Nacional de Ciência e Tecnologia Industrial Avançada (AIST), Japão. Pesquisadora visitante no Departamento de Patologia e Medicina Experimental, Escola de Pós-Graduação em Medicina, Odontologia e Ciências Farmacêuticas, Universidade de Okayama, Japão. Gestora Associada da Divisão de Meio Ambiente e Segurança, Gestão de Bioética e Biossegurança do Instituto Nacional de Ciência e Tecnologia Industrial Avançada (AIST), Japão.
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Nakajima, T., H. Yoshifuji, Y. Yamano, H. Handa, K. Ohmura, T. Mimori e C. Terao. "THU0023 DETAILED PROFILE OF CO-OCCURRENCE OF RELAPSING POLYCHONDRITIS AND AUTOIMMUNE THYROID DISEASE". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 224.2–225. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5349.
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Background:Relapsing polychondritis (RP) is a rare inflammatory disease, which is characterized by recurrent inflammation and destruction of cartilage tissues. RP also has the profile of autoimmune disease and is often complicated with other autoimmune disease. Autoimmune thyroid disease (AITD) is one of common autoimmune diseases, which consists of Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). While RP is reported to be complicated with AITD1), there has been no study on detailed profile of co-occurrence of RP and AITD.Objectives:We aimed to reveal whether there is common (statistically significant) co-occurrence of RP and AITD. We also analyzed clinical and genetic profiles characterizing the co-occurrence.Methods:We recruited 117 patients with RP and checked their medical records in order to obtain the information about compilation of AITD and clinical features. In addition, we genotyped Human Leucocyte Antigen (HLA) A, B Cw, DRB1, DQB1 and DPB1 alleles for 88 of the 117 patients. Co-occurrence ratio was compared with prevalence of AITD in the Japanese population. Associations of co-occurrence of AITD with clinical manifestations or HLA alleles were analyzed among the patients.Results:Among the 117 patients with RP, 5 (4.3%) and 6 (5.1%) patients had GD and HT, respectively. Patients with RP were more likely to be complicated with GD (p=1.04×10-3, OR: 7.15, 95%CI 2.68~ 18.14) but not with HT (p=0.50, 95%CI 0.59~1.27), compared with prevalence in general Japanese population (0.62% and 5.9%, respectively2)). RP patients with GD showed a trend to have nasal involvement (100% vs 45.5%, p=0.023, OR: 2.58, 95%CI 1.09~∞). We did not observe any differences in clinical manifestation in patients with RP and HT. HLA- DPB1*02:02 demonstrated a trend toward GD complication (20% vs 2.3%, p=0.035, OR: 10.41, 95%CI 1.23~65.38). There were no association of HLA in the complication of HT among patients with RP.Conclusion:Patients with RP have high co-occurrence ratio of GD. Patients with the two diseases may be characterized by nasal involvement and HLA-DPB1*02:02.References:[1]Kung AW et al. Graves’ ophthalmopathy and relapsing polychondritis. Clin Exp Rheumatol. 1995 Jul-Aug;13(4):501-3.[2]Nagataki S et al. Thyroid diseases among atomic bomb survivors in Nagasaki. JAMA. 1994 Aug 3;272(5):364-70.Disclosure of Interests:Toshiki Nakajima Speakers bureau: Bristol-Myers Squibb and Novartis, Hajime Yoshifuji Grant/research support from: Astellas Pharma. (Outside the field of the present study.), Speakers bureau: Chugai Pharmaceutical. (Outside the field of the present study.), Yoshihisa Yamano: None declared, Hiroshi Handa: None declared, Koichiro Ohmura Grant/research support from: Astellas Pharma, AYUMI Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Japan Blood Products Organization, Mitsubishi Tanabe Pharma, Nippon Kayaku, Nippon Shinyaku, Sanofi, and Takeda Pharmaceutical., Speakers bureau: AbbVie, Actelion Pharmaceuticals Japan, Asahi Kasei Pharma, AYUMI Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Novartis Pharma, and Sanofi., Tsuneyo Mimori: None declared, Chikashi Terao Grant/research support from: Actelion, Speakers bureau: Asteras, Asahi Kasei Pharma, Ono and Tanabe-Mitsubishi
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Wu, Rongrong, Ankit Patel, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li Yan, Takashi Ishikawa e Kazuaki Takabe. "Abstract 812: High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 812. http://dx.doi.org/10.1158/1538-7445.am2022-812.
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Abstract INTRODUCTION: Homologous recombination deficiency (HRD) is involved in breast cancer carcinogenesis, however, activation of DNA repair in cancer cells may promote its survival and progression. RAD51 plays an essential role in homologous recombination with BRCA2. Recently, RAD51 has been highlighted to play a role in resistance to DNA-damaging chemotherapy or PARP inhibitors. We hypothesized that RAD51 as a prognostic and predictive biomarker of drug sensitivity in breast cancer. MATERIALS AND METHODS: Total of 4500 primary breast cancer patients from three independent cohorts were examined. High and low expression of RAD51 were divided by median RNA expression. Response to treatments were assessed in total of 3000 patients across 11 independent cohorts of breast cancer patients that received neoadjuvant chemotherapy. RESULTS: RAD51 was upregulated in cancer compared to normal tissues in the TCGA cohort and was positively correlated with HRD. Cancer with high RAD51 group enriched DNA repair gene set in gene set enrichment analysis (GSEA) in all cohorts and had high expression of HRD-related genes including BRCA1 and BRCA2. Histological grade and Ki67 expression were positively correlated with RAD51, and all cancer proliferation gene sets from Hallmark (E2F target, G2M checkpoint, Myc Targets v1 and v2, and Mitotic Spindle) were strongly enriched in the high RAD51 expression breast cancer in all cohorts. In TCGA, tumor mutation burden and neoantigen were also higher in tumor with high RAD51 expression, but RAD51 expression was not elevated in BRCA1 or BRCA2 mutant tumors. Cytolytic activity score, a marker of cancer immunity, was elevated high RAD51 group in two cohorts, and the immune cell fraction calculated by the xCell algorithm showed increase in immune cell infiltration, including CD4 memory T cells, Th1 cells, M1 macrophages and activated dendritic cells, in all cohorts, suggesting a certain level of activation of cancer immunity in this RAD51 high breast cancer group. However, contrary to previous reports, RAD51 expression in breast cancer cell lines did not show any association between sensitivity to chemotherapy or PARP inhibitors. Neither for the breast cancer NAC cohort, RAD51 expression was not increased in the residual burden group, but conversely increase in RAD51expression was observed in pathological complete response group in some cohorts. Surprisingly, RAD51 was significantly associated with worse overall survival in all three large cohorts included in this analysis, and with worse disease-specific survival in two cohorts. CONCLUSIONS: RAD51 expression was significantly associated with worse survival, but did not with treatment-responsive, suggesting its usefulness as prognostic, but not predictive, biomarker. Citation Format: Rongrong Wu, Ankit Patel, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li Yan, Takashi Ishikawa, Kazuaki Takabe. High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 812.
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Oshi, Masanori, Shipra Gandhi, Yoshihisa Tokumaru, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo e Kazuaki Takabe. "Abstract P5-03-01: Conflicting roles of EGFR expression by subtypes in breast cancer". Cancer Research 82, n.º 4_Supplement (15 de fevereiro de 2022): P5–03–01—P5–03–01. http://dx.doi.org/10.1158/1538-7445.sabcs21-p5-03-01.
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Abstract Epidermal growth factor receptor (EGFR) is one of the receptors that belongs to the epidermal growth factor family of receptor tyrosine kinases (ErbBs). Several malignancies including breast cancer that express EGFR have poor prognosis. Our study examined the EGFR expression among 5176 breast cancer patients from multiple independent breast cancer cohorts and its contribution to tumor immune microenvironment in different subtypes. We found that, EGFR expression in triple negative breast cancer (TNBC) was the highest among breast cancer subtypes in GSE96058 and METABRIC cohorts when compared to other subtypes (both p < 0.001), which is in agreement with the existing literature. High EGFR expression was significantly associated with improved survival in ER-positive/HER2-negative breast cancer in both cohorts (both p < 0.001) and also significantly associated with high level of intratumor heterogeneity and homologous recombination deficits (HRD) (both p < 0.001) in the TCGA cohort. Furthermore, high EGFR expression tumor enriched not only several pro-cancer-related gene sets, but also immune-related gene sets, including Allograft rejection, inflammatory response, IL2/STAT5 signaling, IL6/JAK/STAT3 signaling, coagulation and complement pathway in both cohorts. On the other hand, low EGFR tumor enriched cell proliferation-related gene sets, including E2F targets, G2M checkpoint MYC targets v1 and v2, and DNA repair, which may explain the observed worse survival (all normal enrichment score < -0.50). However, these findings were not observed in TNBC. Interestingly, high EGFR ER-positive/HER2-negative breast cancers were infiltrated with anti-cancer immune cells (CD8+ T cell, CD4+ T cell, and dendritic cell), and associated with high level of cytolytic activity (CYT) (p < 0.001). On the other hand, a lower fraction of immune cells was observed in high EGFR TNBC along with low level of CYT (p < 0.001). In the single cell sequence data, tumor cells have significantly higher EGFR expression compared to immune cells (p < 0.001). High EGFR expression among ER-positive/HER2-negative breast cancer was significantly associated with higher expression of immune checkpoint molecules (PD-1, PD-L1 and PD-L2, CTLA4, IDO1, and BTLA; all p < 0.001), while, on the other hand, there was lower immune checkpoint molecule expression in high EGFR TNBC. Finally, high EGFR metastatic tumor was associated with worse survival, but there was no association with infiltrating immune cells. In conclusion, EGFR expression was found to have different characteristics depending on breast cancer subtype. Especially, high EGFR ER-positive/HER2-negative breast cancer was significantly associated with better survival and immunity in tumor immune microenvironment. Citation Format: Masanori Oshi, Shipra Gandhi, Yoshihisa Tokumaru, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. Conflicting roles of EGFR expression by subtypes in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-03-01.
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Цраева, Ф. В. "The Life World of a Student Volunteer in the Mechanisms of Culture Reproduction". Nasledie Vekov, n.º 1(33) (31 de março de 2023): 67–81. http://dx.doi.org/10.36343/sb.2023.33.1.006.
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Автор определяет значение, которым обладает жизненный мир студента-волонтера в процессах воспроизводства культуры. Материалами послужили данные, полученные в ходе социологического опроса, проведенного среди студентов Кабардино-Балкарской Республики (КБР), интерпретация которых осуществлена с помощью культурологической атрибуции в трех системах культурных порядков – в трех различных теоретических моделях культуры. В персоноцентричной модели полученные результаты подтверждают положение о противостоянии жизненного мира индивида влиянию социума. В социоцентричной – свидетельствуют о низкой организационно-методической обеспеченности студенческого волонтерского движения в КБР. В бицентричной – определяют направление тренда процесса символизации успеха (персоноцентризм). Установлено, что укрепление персоноцентричных ценностей в жизненном мире индивида ведет к снижению роли волонтерского движения в механизмах воспроизводства культуры, а противоположная тенденция (социоцентризм) ее усиливает. The aim of the study is to reveal the significance of the student-volunteer’s life world in culture reproduction. The life world is understood as a special microspace of personal culture, which is saturated with its own meanings and values. The study is based on data obtained in the course of a sociological survey conducted among students of the Kabardino-Balkaria Republic, Potential of the Volunteer Movement of Students of Universities in Kabardino-Balkaria, as a theoretical basis. Results of studies on the mechanisms of culture reproduction were also used. The methodology consists of methods for collecting and processing empirical data, as well as a methodology for their interpretation developed by the author, based on three concepts: person-centric (based on the phenomenological approach of the European sociological school), socio-centric (using a system-activity approach implemented in domestic cultural studies), and bi-centric (typologies of the socio-cultural process of success symbolization (Gennady Bakumenko)). The theoretical foundations of the conducted sociological survey, based on the methods for studying the motivation for volunteering by Katharina Gaskin and Davis Smith and the model of cross-cultural studies of the third sector of the economy at Hopkins University, are considered in detail, the changes the author made to these methods are described. Three concepts that are the basis for interpreting the results of the study are characterized, differences between them in the interpretation of social reality and the basic mechanisms of cultural reproduction are shown; the author points out that they are, in fact, models of the reproduction of culture. The results of the conducted sociological survey are commented, the significance of the factors influencing the refusal of volunteer activity is determined. The content of the crisis of the inner world of a student volunteer, which is expressed in a change in the value priorities of volunteering in the third year of study at a university, is revealed. The obtained results were interpreted in line with the three models of culture reproduction identified by the author. The life world of a student volunteer is of great importance among the mechanisms of cultural reproduction, since it predetermines the nature of promising trends in sociocultural development. The conclusions of the study were evaluated in the context of the works of scientists analyzing the mechanisms of reproduction of modern culture (Anthony Lyons and Yoshihisa Kashima, Yuuze Zhu and Junmin Liu).
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Wu, Rongrong, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li yan, Takashi Ishikawa e Kazuaki Takabe. "Abstract P2-23-13: Highly proliferative estrogen receptor-positive breast cancer is associated with better response to neoadjuvant chemotherapy but worse clinical outcome". Cancer Research 83, n.º 5_Supplement (1 de março de 2023): P2–23–13—P2–23–13. http://dx.doi.org/10.1158/1538-7445.sabcs22-p2-23-13.
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Abstract Introduction: Highly proliferative cancers are known to respond better to neoadjuvant chemotherapy (NAC), and pathological complete response (pCR) is a surrogate for survival benefit in breast cancer. Ki67 is the most commonly used cell proliferation marker; however, conventional immunostaining is subjected to variability by the assessor and the institution including the antibody used. To this end, we used the Ki67 gene expression to identify highly proliferative breast cancer and investigated whether it is associated with better response to NAC and survival by intrinsic subtype. Materials and Methods: Total of 6623 breast cancer patients from 11 independent cohorts with full transcriptome and clinical data were analyzed. The top 20% of Ki67 gene expression in each cohort were defined as highly proliferative group based on previous studies using immuno-staining. Results: Highly proliferative breast cancer was associated with high proliferation score, and all five cell proliferation-related gene sets in the Hallmark collection; E2F Targets, G2M Checkpoint, Mitotic Spindle, and Myc Targets v1 and v2 were enriched by gene set enrichment analysis in multiple cohorts regardless of subtype. MKI67 gene expression increased with higher grade in both ER-positive breast cancer and TNBC in multiple cohorts, but no clear association with staging was observed. Highly proliferative ER-positive breast cancer was significantly associated with worse disease-free, disease-specific, and overall survival consistently in METABRIC and GSE96058 cohorts, and showed a trend toward worse overall survival in TCGA; however, this was not the case in TNBC. Further, we found that highly proliferative tumor was significantly associated with better pathologic complete response (pCR) rate in six of the eight neoadjuvant chemotherapy cohorts of ER-positive breast cancer, but only two for TNBC. We also found that highly proliferative ER-positive breast cancer was associated with abundant silent and non-silent mutations, increased intra-tumoral heterogeneity, and homologous recombination defect scores when compared to lower proliferation groups, and this was not seen in TNBC in TCGA cohort. Although DNA repair gene set was enriched in the highly proliferative ER-positive breast cancer, it was also associated with higher neoantigen activity, higher infiltration of tumor infiltrating lymphocytes including Th1 cells, Th2 cells, regulatory T cells, and M1 macrophages, as well as with enrichment of Interferon-gamma response gene set consistently in 3 large cohorts. In contrast, several stromal cell fractions were decreased in this group. Conclusions: Highly proliferative ER-positive breast cancer is significantly associated with pCR after NAC with increased tumor infiltrating lymphocytes, but is not a surrogate for survival, which are not the case in TNBC. Citation Format: Rongrong Wu, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li yan, Takashi Ishikawa, Kazuaki Takabe. Highly proliferative estrogen receptor-positive breast cancer is associated with better response to neoadjuvant chemotherapy but worse clinical outcome [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-13.
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TANIGUCHI, Tetsuro. "Mourn over Professor Yoshihito Taniike". Wind Engineers, JAWE 41, n.º 3 (2016): 257–58. http://dx.doi.org/10.5359/jawe.41.257.
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Geppert, L. "Yoshihiro Kuroki: Dancing With Robots". IEEE Spectrum 41, n.º 2 (fevereiro de 2004): 34–35. http://dx.doi.org/10.1109/mspec.2004.1265131.
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Watanabe, M., K. Nishida, Y. Nasu, R. Nakahara, M. Matsuhashi, Y. Hotta e T. Ozaki. "SAT0023 THE ROLE OF ADAM12 UPREGULATED PROLIFERATION OF SYNOVIAL MEMBRANE IN RHEUMATOID ARTHRITIS". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 941.2–942. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1968.
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Background:ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of a variety of tumors by degrading ECM and shed precursors, thus promoting cell proliferation, invasion, and metastasis1). Additionally, ADAM12 is involved in chondrocyte differentiation from osteoarthritis (OA) patients by regulation of TGFβ1-induced IGF-1 and RUNX-2 expressions2). However, there is no report on the role of ADAM12 for rheumatoid arthritis (RA).Objectives:To investigate the expression and role of ADAM12 in the synovial tissue of RA.Methods:(1) The expression of ADAM12 in synovial tissues from RA (18 cases), OA (5 cases) and healthy control (HC) (3 cases) was examined by immunohistochemistry. The synovial tissues of HC were obtained during surgery of hemiarthroplasty for bone tumors. Three researchers evaluated the positive cell ratio. The samples were scored according to the percentage of positive staining: 0 points (weak positive, positive expression was less than 5%), 1 point (moderate positive, positive expression was between 5% and 50%) and 2 points (strong positive, positive expression was greater than 50%). In addition, the samples were scored according to the staining intensity: 0 points (weak intensity), 1 point (moderate intensity) and 2 points (high intensity). (2) The cultured synovial fibroblasts obtained from RA patients at the surgery (RASF) were stimulated by TNFα (1, 5, 10 ng/mL), TGFβ1 (1, 5, 10 ng/mL), PDGF-BB (1, 5, 10 ng/mL) and TNFα+TGFβ1+PDGF-BB (all 10 ng/mL), and the expression levels of ADAM12 relative mRNA was examined by real-time PCR. (3) siADAM12 was transfected in RASF, and the proliferation was examined by WST-1 assay, and the expression of ADAM12 protein was examined by western blotting.Results:(1) ADAM12 positive cells were found in synovial lining cells, plasma cells, and vascular endothelial cells. ADAM12 was highly expressed in RA synovial tissues. The immunostaining scores of RA, OA, and HC were 3.9±0.01, 1.9±0.27, and 0.8±0.18, respectively. (2) Stimulation by TNFα, TGFβ1, and PDGF-BB resulted in the upregulation of the expression of ADAM12 relative mRNA in RASF, and TGFβ1 stimulation notably tended to increase the expression by about 5 to 6 times. (3) siADAM12 successfully suppressed the expression of ADAM12 protein and simultaneously suppressed the proliferation of RASF.Conclusion:ADAM12 might be involved in the pathogenesis of RA, promoting the cell proliferation of RASF.References:[1] Kyeiborg M, Albrechtsen R, Couchman J, et al., Cellular roles of ADAM12 in health and disease, Int J Biochem Cell Biol, 2008[2] Masahiro H, Keiichiro N, Joe H, et al., Involvement of ADAM12 in Chondrocyte Differentiation by Regulation of TGF-beta1-Induced IGF-1 and RUNX-2 Expressions, Calcif Tissue Int, 2019Disclosure of Interests:Masahito Watanabe: None declared, Keiichiro Nishida Grant/research support from: K. Nishida has received scholarship donation from CHUGAI PHARMACEUTICAL Co., Eisai Co., Mitsubishi Tanabe Pharma and AbbVie GK., Speakers bureau: K. Nishida has received speaking fees from CHUGAI PHARMACEUTICAL Co., Eli Lilly, Janssen Pharmaceutical K.K., Eisai Co. and AYUMI Pharmaceutical Corporation., Yoshihisa Nasu: None declared, Ryuichi Nakahara: None declared, Minami Matsuhashi: None declared, Yoshifumi Hotta: None declared, Toshifumi Ozaki: None declared
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Oshi, Masanori, Shipra Gandhi, Michelle R. Huyser, Yoshihisa Tokumaru, Li Yan, Rongrong Wu, Akimitsu Yamada, Itaru Endo e Kazuaki Takabe. "Abstract P1-08-17: Melk expression is associated with immune cell infiltration and pathological compete response (pcr) after neoadjuvant chemotherapy in breast cancer". Cancer Research 82, n.º 4_Supplement (15 de fevereiro de 2022): P1–08–17—P1–08–17. http://dx.doi.org/10.1158/1538-7445.sabcs21-p1-08-17.
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Abstract In experimental settings, maternal embryonic leucine zipper kinase (MELK), an apical member of the snf1/AMPK serine-threonine kinases family, is highly expressed in several malignancies, and plays a role in cell cycle and proliferation in cell culture settings. However, there is no clear insight on the underlying mechanism or association of MELK expression with several key players in the tumor microenvironment (TME) in regulating cancer progression and response to several drugs in the human tumor. We investigated the clinical relevance of MELK expression by performing silico analyses of 7,135 breast cancer patients using multiple independent large cohorts in this study. We found that MELK expression was significantly correlated with tumor growth assessed by American Joint Committee Cancer (AJCC) stage (p < 0.001), Nottingham histological grade (both p < 0.001), MKI67 expression (spearman rank correlation (r) = 0.704 and 0.888, respectively, both p < 0.001), triple-negative breast cancer (TNBC) subtype (both p < 0.001) and also with cell proliferation-related gene sets (all normalized enrichment score (NES) > 1.70, all false discovery rate (FDR) < 0.01) using gene set enrichment analysis (GSEA), in two large cohorts METABRIC and GSE96058. Furthermore, we observed worse patient survival (both p < 0.001), high mutation rate (all p < 0.03), and enhanced cancer cell survival pathways, including MTORC1 signaling, DNA repair and unfolded protein response (all NES > 1.50) in high MELK expression breast cancer. Additionally, breast cancer with high MELK expression was significantly enriched in immune-related gene sets, including allograft rejection, interferon (IFN)-α response and IFN-γ response (all NES > 1.30). Furthermore, infiltration of anti-cancer immune cells (CD4+ memory T cells, T helper type1 cells, CD8+ T cells, M1 macrophages, gamma-delta T cells, and dendritic cells) and pro-cancer (T helper type 2 cells and regulatory T cells), calculated by xCell algorithm, was associated with high MELK expression. High immune cell killing activity (CYT) was also significantly associated with high MELK expression. Although MELK expression did not correlate with sensitivity of any drug tested in cell lines, high MELK was significantly associated with high pathological complete response (pCR) rate after neoadjuvant chemotherapy (NAC) not only in TNBC (area under the curve (AUC) = 0.78, 0.81, and 0.93, respectively), the aggressive breast cancer subtype known to be associated with around 30-40% pCR, but also in ER-positive plus HER2-negative breast cancer (AUC = 0.62, 0.75, and 0.80, respectively), a subtype of breast cancer where pCR rates are very low, in three cohorts GSE25066, GSE20194 and HESS cohorts. In conclusion, our study shows that high MELK expression is significantly associated with cell proliferation, immune cell infiltration, and higher incidence of response to NAC both in ER-positive/HER2-negative and TNBC. Citation Format: Masanori Oshi, Shipra Gandhi, Michelle R Huyser, Yoshihisa Tokumaru, Li Yan, Rongrong Wu, Akimitsu Yamada, Itaru Endo, Kazuaki Takabe. Melk expression is associated with immune cell infiltration and pathological compete response (pcr) after neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-17.
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Ukai, Junko, Yoshihisa Tokumaru, Masanori Oshi, Yoshimi Niwa, Ryutaro Mori, Kazuaki Takabe e Manabu Futamura. "Abstract P4-02-28: EMP1 low expressing tumor is associated with cell proliferation and poor overall survival of ER-positive breast cancer patients". Cancer Research 83, n.º 5_Supplement (1 de março de 2023): P4–02–28—P4–02–28. http://dx.doi.org/10.1158/1538-7445.sabcs22-p4-02-28.
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Abstract Background: Epithelial membrane protein 1 (EMP1) belongs to PMP22 gene family and is reported to be expressed low in numerous gastrointestinal cancers. However, little is known about its role in breast cancer. EMP1 functions to promote cell proliferation. In this study, we hypothesized that low EMP1 expressing breast cancer is associated with high proliferative characteristics and poor survival. Material and Methods: The clinicopathological data and transcriptome data of breast cancer patients from two independent large publicly available databases, The Cancer Genome Atlas (TCGA, n = 1090) and The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC, n = 1904), were utilized in the current study. Survival analyses; Overall survival (OS), Disease-specific survival (DSS) and Disease-free survival (DFS) were performed by comparing the high and low expression groups. CYT score, xCell, and other immunological factors were used to evaluate intratumoral immune cell composition. Also, gene set enrichment analysis (GSEA) was performed between EMP1 high and low expression groups. Results: We divided each cohort into EMP1 expression high and low groups by utilizing median cutoff. The expression levels of EMP1 were not associated with clinical stage in any subtypes. However, interestingly lower expression of EMP1 was significantly associated with more advanced grades in ER positive/HER2 negative (ER+/HER2) subtype in both TCGA and METABRIC cohorts (p< 0.001 and p< 0.001, respectively). Also, low EMP1 expressing tumors demonstrated higher MKI67 expression levels in ER+/HER2- subtype consistently in both TCGA (p< 0.001) and METABRIC cohorts (p< 0.001). Furthermore, GSEA demonstrated that low EMP1 expressing tumors enriched the gene sets associated with cell proliferation such as MYC Targets, E2F signaling, and G2M Checkpoint signaling, compared with low EMP1 expressing tumors in ER+/HER2- of both TCGA and METABRIC cohorts. On the contrary, high EMP1 expressing tumors enriched the immune related gene sets such as Coagulation, Inflammatory_Response, Complement, and IL-6_JAK_STAT3 Signaling in ER+/HER2- of both TCGA and METABRIC cohorts. To this end, we further hypothesized that high EMP1 tumors were associated with favorable tumor immune microenvironment (TIME) and analyzed TIME utilizing xCell. However, to our surprise high EMP1 expressing tumors were not associated with favorable TIME. Low EMP1 expressing tumors demonstrated worse DFS, DSS, and OS compared with high EMP1 expressing tumors in ER+/HER2- breast cancer patients (p=0.013, p=0.003, and p=0.006) which was not the case in the other subtypes in METABRIC cohort. Conclusion: Low EMP1 expressing tumors were associated with improved OS, DSS, DFS in ER-positive breast cancer patients. Also, low EMP1 expressing tumors were found to associate with advanced grades and enriched gene sets related to cell proliferation and cell cycle, which may explain the poor survival of patients with low EMP1 expressing ER+/HER2- breast cancer. Citation Format: Junko Ukai, Yoshihisa Tokumaru, Masanori Oshi, Yoshimi Niwa, Ryutaro Mori, Kazuaki Takabe, Manabu Futamura. EMP1 low expressing tumor is associated with cell proliferation and poor overall survival of ER-positive breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-28.
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Tokumaru, Yoshihisa, Rongrong Wu, Junko Ukai, Masanori Oshi, Yoshimi Niwa, Ryutaro Mori, Kazuaki Takabe e Manabu Futamura. "Abstract P4-02-03: Transcriptomic signature score of Epithelial-Mesenchymal Transition (EMT) of a bulk tumor may not reflect that of cancer cells". Cancer Research 83, n.º 5_Supplement (1 de março de 2023): P4–02–03—P4–02–03. http://dx.doi.org/10.1158/1538-7445.sabcs22-p4-02-03.
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Abstract Background: Epithelial-mesenchymal transition (EMT) is a well-known multistep process of cancer cell invasion and metastasis, as well as treatment resistance. Our group has been reporting the predictive role of scores generated using Gene Set Variation Analysis (GSVA) of Hallmark pathways in breast cancer. In this study, we hypothesized that EMT score high breast cancer is aggressive and is associated with poor clinical outcome. Material and Methods: The clinicopathological data and transcriptome data of breast cancer patients from three independent large publicly available databases, The Cancer Genome Atlas (TCGA, n = 1077), The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC, n = 1904), and GSE96058 (n=3069) were utilized. Survival analyses; Overall survival (OS), Disease-specific survival (DSS) and Disease-free survival (DFS) were performed by comparing the high and low score groups. Tumor immune microenvironment was analyzed utilizing the values reported by Thorsson et al. Also, single sample Gene Set Enrichment analysis (ssGSEA) was performed between EMT high and low expression groups utilizing singe cell sequence cohorts. Results: EMT score was generated by Gene Set Variation Analysis of a Hallmark gene set and we divided each cohort into EMT score high and low groups by utilizing median as the cutoff. To our surprise, EMT score of the primary tumor was not associated with metastasis (N and M categories of cancer staging), Nottingham histological grade, nor MKI67 expression levels consistently in TCGA, METABRIC, and GSE96058. EMT score high tumors were not associated with worse DFS, DSS, OS in TCGA and METABRIC and OS in GSE96058. Analyses using xCell demonstrated that EMT score high tumors were associated with high infiltration of stromal cells such as adipocyte (p< 0.001, p< 0.001 and p< 0.001, respectively) and fibroblasts (p< 0.001, p< 0.001 and p< 0.001, respectively) in all three cohorts, TCGA, METABRIC, and GSE96058. Also, myeloid cells such as macrophages (p< 0.001, p< 0.001 and p< 0.001, respectively) and dendritic cells (p< 0.001, p< 0.001 and p< 0.001, respectively) were highly infiltrated with EMT score high tumors. Result of ssGSEA of single cell sequence cohorts revealed that cancer associated fibroblasts demonstrated highest EMT scores compared with the other cell types such as cancer cells, T-cells, B-cells, or myeloid cells. In other words, EMT score of a bulk tumor may reflect the signature from fibroblasts rather than cancer cells. Conclusion: We found that cancer associated fibroblasts rather than cancer cells are the major source of the transcriptomic signatures of EMT in the bulk tumor, which cautions us to be careful with the interpretation of the results of EMT signature from a bulk tumor. Citation Format: Yoshihisa Tokumaru, Rongrong Wu, Junko Ukai, Masanori Oshi, Yoshimi Niwa, Ryutaro Mori, Kazuaki Takabe, Manabu Futamura. Transcriptomic signature score of Epithelial-Mesenchymal Transition (EMT) of a bulk tumor may not reflect that of cancer cells [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-03.
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Nomura, Kotaro, Shogo Kumagai, Shohei Koyama, Keiju Aokage, Yoshihisa Shimada, Kiyotaka Yoh, Masashi Wakabayashi et al. "Abstract 1211: Biomarker analysis of pembrolizumab and ramucirumab neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer: EAST ENERGY trial". Cancer Research 84, n.º 6_Supplement (22 de março de 2024): 1211. http://dx.doi.org/10.1158/1538-7445.am2024-1211.
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Abstract Background: Neoadjuvant treatments with novel combination immunotherapies for resectable non-small cell lung cancer (NSCLC) are being developed. Combination therapy with antiangiogenic agents and anti-PD-1/PD-L1 antibody has shown enhanced antitumor effects. EAST ENERGY is a single-arm multicenter phase 2 trial of neoadjuvant pembrolizumab and ramucirumab in patients with PD-L1-positive stage IB-IIIA NSCLC (NCT04040361). In this study, we aimed to identify biomarkers that predicts the efficacy of the neoadjuvant therapy. Furthermore, we aimed to elucidate the effect of the neoadjuvant therapy on the tumor microenvironment (TME). Methods: Patients enrolled in the EAST ENERGY trial (n=24) for whom pre- and post-treatment specimens were available (n=20) were included in this study. RNA-sequencing and multiplex immunohistochemistry (mIHC) were used to examine the association between the immunological phenotype of the TME and major pathological response (MPR), and changes in the TME before and after treatment. Results: MPR was achieved in 50.0% (12/24) of patients. Biomarker analyses with RNA-sequencing revealed that high expression of cancer-associated genes, and upregulation of interferon-gamma and interferon-alpha response in pre-treatment tumor were associated with MPR (q value<0.001). mIHC in pre-treatment samples revealed that abundance of CD8+ T cells in the pre-treatment TME was associated with MPR (p=0.039). On the other hand, infiltration of immunosuppressive cells such as Treg or M2-macrophages were not associated with resistance for the treatment (p=0.836, 0.639, respectively). Next, to clarify the effect of the neoadjuvant therapy on the TME, comparative analyses of pre- and post-treatment samples was performed. In gene set enrichment analysis, the neoadjuvant therapy enhanced gene set associated with interferon-gamma response (q value=0.051). Furthermore, angiogenesis-related gene set were downregulated after the treatment (q value=0.090). mIHC analyses revealed that the number of CD8+ T cells in the TME was significantly increased after the neoadjuvant therapy (p<0.001). Notably, Tregs/CD8+ T cells ratio and the number of M2-macrophage in the TME were significantly decreased after the neoadjuvant therapy (p=0.032, 0.003, respectively). Conclusion: In the neoadjuvant therapy with pembrolizumab and ramucirumab, immune-activated status before treatment serves as a potential biomarker for predicting treatment response. Moreover, combining ramucirumab with pembrolizumab reduced immunosuppressive cells in the TME and inhibited tumor angiogenesis. These results suggest that this combination therapy modifies the TME and augments antitumor immunity. Larger clinical trial is warranted to assess the efficacy of neoadjuvant therapy with ramucirumab and pembrolizumab in patients with PD-L1-positive NSCLC. Citation Format: Kotaro Nomura, Shogo Kumagai, Shohei Koyama, Keiju Aokage, Yoshihisa Shimada, Kiyotaka Yoh, Masashi Wakabayashi, Miki Fukutani, Hideki Furuya, Tomohiro Miyoshi, Kenta Tane, Joji Samejima, Tetsuro Taki, Takuo Hayashi, Jun Matsubayashi, Genichiro Ishii, Norihiko Ikeda, Hiroyoshi Nishikawa, Masahiro Tsuboi. Biomarker analysis of pembrolizumab and ramucirumab neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer: EAST ENERGY trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1211.
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Asao, Yoshihiko. "Suffixing Preferences as a Consequence of Probabilistic Reasoning Yoshihiko Asao". LSA Annual Meeting Extended Abstracts 4 (7 de maio de 2013): 4. http://dx.doi.org/10.3765/exabs.v0i0.778.
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Kumagai, Shinji, e Shoji Kubo. "Photoinitiators enhanced 1,2-dichloropropane-induced cytotoxicity in human normal embryonic lung fibroblasts cells in vitro, Yoichi Kawasaki, Chiaki Tsuboi, Kenta Yagi, Miwa Morizane, Yasuyuki Masaoka, Satoru Esumi, Yoshihisa Kitamura, Toshiaki Sendo (2014) Environ Sci Pollut Res 22: 4763-4770 ; DOI: 10.1007/s11356-014-3939-8". Environmental Science and Pollution Research 23, n.º 7 (13 de fevereiro de 2016): 7067–68. http://dx.doi.org/10.1007/s11356-016-6165-8.
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Tsujimoto, Yoshihiro, Jun J. Li, Kazunari Yamaura, Yoshitaka Matsushita, Yoshio Katsuya, Masahiko Tanaka, Yuichi Shirako, Masaki Akaogi e Eiji Takayama-Muromachi. "Correction: New layered cobalt oxyfluoride, Sr2CoO3F". Chemical Communications 52, n.º 86 (2016): 12777. http://dx.doi.org/10.1039/c6cc90459a.
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Bonetta, Laura. "Profile of Yoshihide Hayashizaki, M.D., Ph.D." BioTechniques 38, n.º 3 (março de 2005): 339. http://dx.doi.org/10.2144/05383sp01.
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Kato, Harubumi. "In memoriam: Yoshihiro Hayata (1924–2012)". General Thoracic and Cardiovascular Surgery 62, n.º 4 (28 de fevereiro de 2014): 205–6. http://dx.doi.org/10.1007/s11748-013-0364-8.
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Kubozono, Yoshihiro, Keita Hyodo, Hiroki Mori, Shino Hamao, Hidenori Goto e Yasushi Nishihara. "Correction: Transistor application of new picene-type molecules, 2,9-dialkylated phenanthro[1,2-b:8,7-b′]dithiophenes". Journal of Materials Chemistry C 3, n.º 12 (2015): 2960. http://dx.doi.org/10.1039/c5tc90044a.
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Correction for ‘Transistor application of new picene-type molecules, 2,9-dialkylated phenanthro[1,2-b:8,7-b′]dithiophenes’ by Yoshihiro Kubozono et al., J. Mater. Chem. C, 2015, 3, DOI: 10.1039/c4tc02413c.
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Kinoshita, M., Y. Kaneko, M. Watanabe, Y. Imai, S. Shrestha, J. Suwa, Y. Ohishi et al. "OP0306 CD11C-SPECIFIC ABLATION OF SHP1 INDUCES AUTOIMMUNE SIALADENITIS SIMILAR TO SJÖGREN’S SYNDROME". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 189.1–190. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1044.
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Background:Dendritic cells (DCs) play important roles in inducing immune response as well as maintaining immune tolerance. Src homology 2 domain-containing protein tyrosine phosphatase-1 (Shp1) is a negative regulator of signaling in hematopoietic cells and is expressed in a variety of immune cells including DCs. Shp1 homozygous mutant mice (motheaten mice) develop multiple immunological abnormalities and they die around four weeks after birth because of severe pneumonitis. Motheaten mice produce large amounts of autoantibodies, and besides, B-1a cells, a distinct B cell subset, which are an important source of autoantibodies increase in these mice. The functional abnormality of DCs in motheaten mice has not been characterized, but DCs and macrophages increase in various organs of motheaten mice.To analyze the function of Shp1 in DCs, we generated Shp1 conditional knockout mice (Shp1 CKO) in whichShp1gene is specifically depleted in CD11c+cells. We found that aged shp1 CKO developed autoimmune glomerulonephritis. We also found that they developed severe tubulointerstitial nephritis (TIN) at the age of 40 weeks, which is characterized by the infiltration of CD11c+and F4/80+cells. CD4+T cells from Shp1 CKO produce much more amount of IFNγ. Collectively, Shp1 in DCs acts as a key regulatory molecule to protect against autoimmunity.Objectives:We analyzed salivary glands of CKO to confirm whether they have autoimmune sialadenitis because TIN is known to be the most common renal manifestations of Sjögren’s syndrome in human.Methods:Shp1 CKO are generated by crossing a mouse line carrying floxedShp1allele to mice expressing Cre recombinase under the control of the CD11c promoter. Sex- and age-matchedPtpn6fl/fllittermates withoutCregene were studied as controls. We analyzed secretory function of the salivary glands in response to pilocarpine stimulation in Shp1 CKO at the age of 40 weeks or older. We then performed histological examination of salivary glands (submandibular glands and sublingual glands) with light-microscopy and immunohistochemical staining. The mononuclear cells prepared from the salivary glands were analyzed by flow cytometry (FCM). We also quantified anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies by ELISA.Results:Shp1 CKO secreted less saliva flow compared to control mice by pilocarpine stimulation. Histological study showed Shp1 CKO exhibited massive infiltration of inflammatory cells in salivary glands associated with periductal foci and periductal fibrosis. Most of infiltrated cells were stained by anti- CD4 or B220 mAbs. FCM revealed that B cells increased in the salivary glands of Shp1 CKO. In addition, B-1a cells also increased in the salivary glands of the mice. The levels of anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies were increased in Shp1 CKO.Conclusion:CD11c-specific ablation of Shp1 induces the ectopic generation of lymphoid structure in salivary glands and impairment of salivary secretion. Autoantibody profile in Shp1 CKO resembled that in human Sjögren’s syndrome. Our findings suggest that aged Shp1 CKO have the potential to become a new mouse model for the analysis of Sjögren’s syndrome.References:[1]Green C. M. et al. J Heredity. 1975; 250-258.[2]Kaneko T. et al. J Immunology. 2012; 5397-540.[3]Watanabe M. et al. Biochem Biophys Rep. in press.Disclosure of Interests:Masato Kinoshita: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Mitsuharu Watanabe: None declared, Yoichi Imai: None declared, Shreya Shrestha: None declared, Junya Suwa: None declared, Yuko Ohishi: None declared, Hiroko Hamatani: None declared, Masao Nakasatomi: None declared, Toru Sakairi: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Yoshihisa Nojima: None declared, Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.
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Okita, S., R. Nakahara, M. Matsuhashi, M. Watanabe, Y. Nasu, K. Nishida e T. Ozaki. "AB0216 POWER DOPPLER SCORE IS USEFUL TO PREDICT JOINT DESTRUCTION OF HAND AND WRIST JOINT IN RHEUMATOID ARTHRITIS PATIENTS." Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 1408.1–1409. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2146.
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Background:Several studies demonstrated that total power Doppler (PD) signal can predict radiographic progression as a change in total van der Heijde-modified total Sharp score (mTSS) in rheumatoid arthritis (RA) patients. However, in some studies, radiographic progression was observed in a different joint compared with the site of a positive PD signal at baseline in many cases.Objectives:The aim of this study was to identify the clinical factor of RA patients in association with radiographic progression of hands and wrists and to investigate which joint showed radiographic progression in RA patients. We focused on the correlation of the site of a positive PD signal and the site of radiographic progression.Methods:We examined retrospectively of 70 RA patients (67 women, three men) who underwent ultrasonography (US) examination at 32 regions on bilateral hands and wrists from 2014 to 2016. Radiographs of the hands were taken at baseline and at least one year after US (mean, 19.9 months), and radiographic progression was assessed using mTSS system. We performed multivariate logistic regression analysis to investigate the association between baseline factors and radiographic progression. The relationships between radiographic progression of the individual joint and total/each joint PD score were assessed by ROC analysis and Fisher’s exact test.Results:Nineteen patients (37.3%) experienced progression of mTSS of hands and wrists. DAS28-CRP (P=0.02) and total PD score (P=0.01) were associated with radiographic progression, and total PD score was significantly associated with radiographic progression (OR 1.22; 95% CI 1.04-1.36; P=0.006) by multivariate logistic regression analysis (Table 1).Table 1.Association between the demographic and clinical findings at baseline and radiographic progression over 12 monthsa.univariate analysisNo radiographicprogression(n = 51)Radiographicprogression(n = 19)P-valueAge, years63.4 ± 12.758.1 ± 10.60.61Duration of RA, years24.4 ± 13.620.0 ± 5.00.28Usage of Bio, %42.240.40.57Amount of MTX, mg/week4.8 ± 3.34.5 ± 4.30.77Amount of PSL, mg1.5 ± 2.11.8 ± 2.20.73DAS28-CRP2.5 ± 0.72.9 ± 0.60.02*CRP, mg/dl0.4 ± 0.50.7 ± 0.70.10Total PD score2.4 ± 3.36.6 ± 6.10.01*b.multivariate analysisodds ratio95% CIP-valueDAS28-CRP1.630.72 - 3.710.238Total PD score1.191.04 - 1.360.010*Predictive performance of total PD score was good for radiographic progression of MCP joint (AUC-ROC 0.91) and wrist joint (AUC-ROC 0.85), although poor for PIP joint (AUC-ROC 0.57).PD score of wrist joint, MCP joint, and PIP joint were significantly associated with radiographic progression of each joint (P<0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of wrist joint PD score were 100%, 57.0%, 8.0%, and 100%, MCP joint PD score were 85.7%, 90.5%, 8.0%, 99.8%, and 8.3%, and PIP joint PD score were 30.0%, 97.2%, 13.6%, and 99.0%, respectively.Conclusion:Total PD score of hands and wrists was a strong predictor of radiographic progression, especially in MCP and wrist joint. Evaluation of PD signal in individual joint is a clinically useful method to predict radiographic progression of the same joint, however there are some differences in sensitivity and specificity.References:[1]Brown AK, et al. Arthritis & Rheumatism. 2008;58:2958-2967.[2]McQueen F, et al. Annals of the Rheumatic Diseases. 2011;70:241-244.Disclosure of Interests:Shunji Okita: None declared, Ryuichi Nakahara: None declared, Minami Matsuhashi: None declared, Masahito Watanabe: None declared, Yoshihisa Nasu: None declared, Keiichiro Nishida Grant/research support from: K. Nishida has received scholarship donation from CHUGAI PHARMACEUTICAL Co., Eisai Co., Mitsubishi Tanabe Pharma and AbbVie GK., Speakers bureau: K. Nishida has received speaking fees from CHUGAI PHARMACEUTICAL Co., Eli Lilly, Janssen Pharmaceutical K.K., Eisai Co. and AYUMI Pharmaceutical Corporation., Toshifumi Ozaki: None declared
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Zayonchkovskiy, Vyacheslav S., Aung Kyaw Kyaw, Igor M. Milyaev, Nikolay S. Perov, Igor A. Prokhorov, Alexey A. Klimov e Alexey A. Andreev. "Тонкие металлические пленки с дисперсионно-твердеющими магнитными слоями сплава Fe–Cr–Co". Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 21, n.º 4 (19 de dezembro de 2019): 505–18. http://dx.doi.org/10.17308/kcmf.2019.21/2362.
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Магнетронным напылением на кремниевые монокристаллические подложки получены трехслойные пленки, содержащие слой дисперсионно-твердеющего сплава (СДТС) на основе системы Fe-Cr-Co. Установлено, что толщина слоя меди, который обеспечивает сохранность дисперсионно-твердеющего сплава СДТС на подложке после отжига, должна быть не менее толщины дисперсионно-твердеющего сплава СДТС. Построена зависимость радиуса изгиба образцов подложек со структурами от температуры изохронного отжига и определены критические температуры и радиусы изгиба, приводящие к разрушению пленок после такого отжига, для различных толщин дисперсионновердеющего сплава СДТС. Получена зависимость коэрцитивной силы (КС) пленок от температуры изохронного отжига, которая при определенных условиях отжига превышает уровень,необходимый для применения этих пленок в магниторезистивных датчиках тока. Сделан вывод о том, что рост коэрцитивной силы КС после отжига связан с образованием выступов в дисперсионно-твердеющем сплаве СДТС.
ЛИТЕРАТУРА1. Masahiro Kitada, Yoshihisa Kamo, Hideo Tanabe. Magnetoresistive thinНfi lm sensor with permanentmagnet biasing fi lm // Journal of Applied Physics, 1985, v. 58(4), pp. 1667–1670. DOI: https://doi.org/10.1063/1.3360582. Leo K. E. B. Serrona, Sugimura A., Fujisaki R., Okuda T., Adachi N., Ohsato H., Sakamoto I., NakanishiA. Magnetic and structural properties of NdFeB thin fi lm prepared by step annealing // Materials Scienceand Engineering B, 2003,v. 97(1), pp. 59–63. DOI: https://doi.org/10.1016/s0921-5107(02)00401-43. Хлопов Б. В., Самойлова В. С., Юрьев И. А. Изменение состояния тонкопленочных слоев маг-нитных материалов, применяемых в системах внешней памяти жестких магнитных дисков //T-Comm: Телекоммуникация и транспорт, 2015, т. 9(12), с. 5–11.4. Коноплёв Ю. В., Изгородин А. К. Структурообразование, свойства и применение горячедеформированных сплавов ЮНДК и ЮНДКТ. Режимдоступа: https://cyberleninka.ru/article/n/strukturoobrazovanie-svoystva-i-primenenie-gorya achedeformirovannyh-splavov-yundk-i-yundkt (датаобращения: 24.10.2019).5. Kaneko H., Homma M., Nakamura K. New ductile permanent magnet of Fe–Cr–Co system // AJP ConferenceProceedings. 1972, no. 5, рp. 1088–1092. DOI: https://doi.org/10.1063/1.29538146. ГОСТ 24897-81. Материалы магнитотвердые деформируемые. Solid magnetic deformed materials.Marks. М.: Издательство стандартов, 1981, 21 с.7. Овсянников Г. А., Петржик А. М., Борисенко И. В., Климов А. А., Игнатов Ю. А., Демидов В. В.,Никитов С. А. Магнитно-транспортные характеристики напряженных эпитаксиальных манганитных пленок La0.7Sr0.3MnO3 // ЖЭТФ, 2009, т. 135(1), с. 56-64.8. Сайт компании ООО «ГЕО-НДТ». Режим доступа: https://www.geo-ndt.ru/pribor-6855-rentgenoflyorescentnii-analizator-metekspert.htm (дата обращения: 20.10.2019)9. Кекало И. Б., Самарин Б. А. Физическое металловедение прецизионных сплавов. Сплавы с особымимагнитными свойствами. M.: Металлургия, 1989, 496 с.10. Справочник по цветным металлам. Режим доступа: https://libmetal.ru/index.htm (дата обращения: 24.10.2019)11. Всё о металлургии. Режим доступа: http://metal-archive.ru/vanadiy/955-mehanicheskiesvoystva-vanadiya.html (дата обращения : 24.10.2019)12. Громов Д. Г. Металлизация ультрабольших интегральных схем. Учебное пособие / Д. Г. Громов,А. И. Мочалов, А. Д Сулимин, В. И. Шевяков. М.: БИНОМ, 2012. 277 с.13. Прохоров И. А., Захаров Б. Г. Рентгенодифракционные исследования особенностей релакса-ции и распределения макронапряжений в эпитаксиальных структурах // Поверхность. Рентгеновские,синхротронные и нейтронные исследования, 1999, № 2, с. 106–109.14. Stouney G. S. The Tension of Metallic Films Deposited by Electrolysis // Proceedings of the RoyalSociety A: Mathematical, Physical and Engineering Sciences, 1909, v. 82(553), pp. 172–175. DOI: https://doi.org/10.1098/rspa.1909.002115. Добрынин В. А. О применимости формулы Стоуни для расчета механических напряжений втолстых пленках и покрытиях // Письма в ЖТФ, 1997, т. 23, № 18, с. 32–36.16. Громов Д. Г. Размерный эффект плавления в пленочных структурах наноэлектроники // Нанотехнологии в электронике. Выпуск 2: Сб. науч. тр. М.: Техносфера, 2013, с. 136–177.17. Громов Д. Г., Гаврилов С. А., Редичев Е. Н., Аммосов Р. М. Кинетика процессов плавления-диспергирования тонких пленок меди // ФТТ, 2007, т. 49(1), с. 173-177.
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Das, Gokul M., Chetan C. Oturkar, Christina Adams, Jung H. Park, Melissa Dolan, Michalis Mastri, Manasori Oshi et al. "Abstract 3986: Combination of tamoxifen and doxorubicin targets estrogen receptor beta-mutant p53-p73 axis: A novel therapeutic strategy for triple negative breast cancer". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 3986. http://dx.doi.org/10.1158/1538-7445.am2022-3986.
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Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype without any effective targeted therapies and rapidly become resistant to generic chemotherapy. Therefore, there is an urgent need to develop new therapeutic strategies. Estrogen receptor beta (ER beta) levels are high in about 60-70% of TNBCs. Recent reports including the Cancer Genome Atlas (TCGA) show that about 80% of TNBC express mutant p53 and it is the most predominant driver in these cancers. We have previously reported (JNCI, 2019, 111:1202-1215) that ER-beta binds p53 and exerts proliferative versus anti-proliferative/tumor suppressive functions depending on the wild type and mutant p53 status in TNBC, respectively. In the current work we used multiple approaches such as immunoprecipitation, in situ proximity ligation assay (PLA), and gene expression analysis by quantitative real-time PCR (qRT-PCR) to show that tamoxifen (Tam) increases ER beta-p53 interaction resulting in decrease of mutant p53 binding to p73 leading to cell cycle arrest, increased apoptosis, decreased proliferation, and increased expression of anti-proliferation genes. Importantly, ER beta antagonist PHTPP decreases the ER beta-p53 interaction in TNBC cells, whereas ER beta agonist DPN did not have any effect. Importantly, Tam synergized with doxorubicin (Dox) to decrease the IC50 of Dox more than 3-fold. This synergism was absent in an isogenic cell line where TP53 gene was knocked out. The fact that mutant p53 expression was necessary for Tam to synergize with Dox, along with our observation that upregulation of anti-proliferation gene expression was dependent on both ER beta and p73, strongly suggests that ER beta-mutant p53-p73 axis is the target of the novel effect of Tam. RNA-seq and reverse phase protein array (RPPA) analysis of isogenic TNBC cells differing in p53 mutational status without and with ER beta depletion revealed important cellular pathways impacted by the synergistic effect of Tam plus Dox combination treatment. To test the effect of Tam plus Dox combination therapy in vivo, we used isogenic MDA-MB-231 cell line-derived xenograft (CDX) and TNBC patient-derived xenograft (PDX) tumors. Consistent with our observations in the TNBC cell models, combination therapy inhibited progression of both CDX and PDX tumors more effectively compared to monotherapies. Furthermore, the antitumor effect was dependent on expression of mutant p53 in tumors. Our study has revealed a novel ER beta-mutant p53-p73 axis that could be targeted by Tam in combination with chemotherapy, raising the possibility of repurposing Tam to treat molecularly stratified TNBC that expresses both ERβ and mutant p53. Besides the potential for relatively faster entry of a safe and less expensive therapy to the clinic, our discovery can be exploited to reduce toxic adverse effects by reducing the dose of Dox in treatment regimens. Citation Format: Gokul M. Das, Chetan C. Oturkar, Christina Adams, Jung H. Park, Melissa Dolan, Michalis Mastri, Manasori Oshi, Yoshihisa Tokumaru, Utpal K. Mukhopadhyay, Kalyani Abha, Kwang H. Jung, Sukjin Yang, Suna Kim, John Ebos, Kazuaki Takabe, Benny A. Kaipparettu. Combination of tamoxifen and doxorubicin targets estrogen receptor beta-mutant p53-p73 axis: A novel therapeutic strategy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3986.