162 research outputs found
Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells
No full text博士論文本文Full 以下に掲載：Oncotarget 5(13) pp.4920-1928 2014. Creative Commons. 共著者：Azusa Tanimoto, Tadaaki Yamada, Shigeki Nanjo, Shinji Takeuchi, Hiromichi Ebi, Kenji Kita, Kunio Matsumoto, Seiji Yan
Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells
No full text金沢大学博士（医学）博士論文本文Full 以下に掲載：Oncotarget 5(13) pp.4920-1928 2014. Creative Commons. 共著者：Azusa Tanimoto, Tadaaki Yamada, Shigeki Nanjo, Shinji Takeuchi, Hiromichi Ebi, Kenji Kita, Kunio Matsumoto, Seiji Yanodoctoral thesi
Abstract 4681: Histone deacetylase 3 inhibition overcomes <i>BIM</i> deletion polymorphism-mediated osimertinib resistance in <i>EGFR</i>-mutant lung cancer
No full textAbstract
Purpose:The BIM deletion polymorphism is associated with apoptosis resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, in non-small cell lung cancer (NSCLC) harboring EGFR mutations. Here, we investigated whether the BIM deletion polymorphism contributes to resistance against osimertinib, a third-generation EGFR-TKI. In addition, we determined the efficacy of a histone deacetylase (HDAC) inhibitor, vorinostat, against this form of resistance and elucidated the underlying mechanism.
Experimental Design:We used EGFR-mutated NSCLC cell lines which were either heterozygous or homozygous for the BIM deletion polymorphism to evaluate the effect of osimertinib in vitro and in vivo. Protein expression was examined by western blotting. Alternative splicing of BIM mRNA was analyzed by RT-PCR.
Results:EGFR-mutated NSCLC cell lines with the BIM deletion polymorphism exhibited apoptosis resistance to osimertinib in a polymorphism dosage-dependent manner, and this resistance was overcome by combined use with vorinostat. Experiments with homozygous BIM deletion-positive cells revealed that vorinostat affected the alternative splicing of BIM mRNA in the deletion allele, increased the expression of active BIM protein, and thereby induced apoptosis in osimertinib-treated cells. These effects were mediated predominantly by HDAC3 inhibition. In xenograft models, combined use of vorinostat with osimertinib could regress tumors in EGFR-mutated NSCLC cells homozygous for the BIM deletion polymorphism. Moreover, this combination could induce apoptosis even when tumor cells acquired EGFR-T790M mutations.
Conclusions:These findings indicate the importance of developing HDAC3-selective inhibitors, and their combined use with osimertinib, for treating EGFR-mutated lung cancers carrying the BIM deletion polymorphism.
Note: This abstract was not presented at the meeting.
Citation Format: Azusa Tanimoto. Histone deacetylase 3 inhibition overcomes BIM deletion polymorphism-mediated osimertinib resistance in EGFR-mutant lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4681. doi:10.1158/1538-7445.AM2017-4681</jats:p
Sorafenib treatment for patients with RET fusion-positive non-small cell lung cancer
No full text主査 : 伊豫田明 / タイトル : Sorafenib treatment for patients with RET fusion-positive non-small cell lung cancer / 著者 : Atsushi Horiike, Kengo Takeuchi, Takeshi Uenami, Yuko Kawano, Azusa Tanimoto, Kyohei Kaburaki, Yuichi Tambo, Keita Kudo, Noriko Yanagitani, Fumiyoshi Ohyanagi, Noriko Motoi, Yuichi Ishikawa, Takeshi Horai, Makoto Nishio/ 掲載誌 : Lung Cancer /巻号・発行年等 : 93:43-46, 2016 / 本文ファイル: 出版者
A Passage to the Future
No full text1988/02/01. Confronts deep, traumatic wounds as a Christian with a past. Professor of Christian Education, Azusa Pacific University; author
Early oneness pentacostalism, Garfield Thomas Haywood, and the inter racial pentecostal assemblies of the world (1906-1931)
No full textThis thesis examines Oneness Pentecostalism from 1914 to 1931 via its initial interracial vision, the ministry of Garfield Thomas Haywood, and the Pentecostal Assemblies of the World. It attempts to rectify a one dimensional historical perspective which has ignored the significance of race in the restorative framework of the early movement, tracing its interracial fervor to the Azusa revival and its resistance to the Parham influenced U.S.south. Fresh historical detail informs assessment of the 1906 Azusa mission founding of the interracial PAW and Oneness Pentecostalism’s most obscure, yet vital early leaders, J. J. Frazee and E. W. Doak. All key leaders are studied from the perspective of the movement’s major centers, especially the centrality and history of Haywood and Indianapolis as its foremost epicenter. Its interracial authenticity is examined in relationship to its pre-Oneness PAW context, the battle for the Assemblies of God, and the transition of the PAW from Trinitarian to Oneness Pentecostalism. Investigation of the 1924 PAW racial schism, impact, and withdrawing White segment reveals diffusion and the proliferation of separatism and independency. The final analysis summarizes the movement’s region by region development and global spread by 1930 and examines the successes of early Oneness Pentecostal missionaries
ALK融合遺伝子陽性肺癌におけるアポトーシス抵抗性因子の解明と克服治療の開発
No full text未治療のALK融合遺伝子陽性肺癌患者に対するALK阻害薬 (alectinib) の効果とTP53変異との相関関係を明らかにするため、肺がんの臨床情報と遺伝子情報が統合されたデータベースを解析した。その結果、TP53変異陽性群では野生型群よりも有意に無増悪生存期間が短かった。そして、TP53変異を有するALK融合遺伝子陽性肺癌細胞株に対してプロテアソーム阻害薬をalectinibに併用したところ、アポトーシスを強く誘導した。メカニズムとしてプロテアソーム阻害薬がアポトーシス蛋白であるNoxaの分解を阻害し、細胞内で増加したNoxaが抗アポトーシス蛋白であるMcl-1に結合することを見出した。We used integrated clinical and next-generation sequencing data. ALK-rearranged NSCLC cell lines expressing wild-type or mutant TP53 were used to evaluate cellular apoptosis induced by ALK-TKIs.In 90 ALK-rearranged NSCLC patients who were treated with a selective ALK-TKI, alectinib, TP53 co-mutated patients showed significantly worse progression-free survival (PFS) than TP53 wild-type patients [median PFS, 11.7 months vs.NR; p=0.0008; hazard ratio, 0.33]. ALK-rearranged NSCLC cell lines which lost p53 function were resistant to alectinib-induced apoptosis, but a proteasome inhibitior, ixazommib markedly induced apoptosis in the alectinib-treated cells by increasing the expression of a pro-apoptotic protein, Noxa which bound to an anti-apoptotic protein, Mcl-1. In subcutaneous tumor models, combination of ixazomib and alectinib prominently induced tumor regression and apoptosis even though the tumors were generated from ALK-rearranged NSCLC cells with non-functional p53.研究課題/領域番号:18K15922, 研究期間(年度):2018-04-01 – 2021-03-31出典：「ALK融合遺伝子陽性肺癌におけるアポトーシス抵抗性因子の解明と克服治療の開発」研究成果報告書 課題番号18K15922
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18K15922/18K15922seika/）を加工して作成research repor
Mitchell, Dr. Henry H. Interview of Willie Ella Asberry With E.P. Mitchell and Jack Catherill of Sacramento Side 1, Rev. Woody at 216 N. Bonny Brae Side two
No full textDr. Henry Mitchell interviews several people associated with the Pentecostal movement and the Azusa street revival.The Atlanta University Center Robert W. Woodruff Library acknowledges the generous support of the National Endowment for Humanities - Humanities Collections and Reference Resources Implementation Project Grant in supporting the processing and digitization of a number of its major archival collections as part of the project: Spreading the Word: Expanding Access to African American Religious Archival Collections at the Atlanta University Center Robert W. Woodruff Library.</em
Nonvicarious Art: The Psychological Techniques and Phenomena Employed in James Turrell's Experiential Perceptual Cells and Ganzfeld Works
No full textThis paper presents a comprehensive collection and explanation of the many psychological techniques and phenomena that are integrated into the works within James Turrell’s Perceptual Cells and Ganzfeld series. It will provide an experiential analysis of Light Reignfall (2011) from the former, and Breathing Light (2013) from the latter, as examples for why the author argues that these works demand a redefinition of the art object and the term “viewer”. The author also presents evidence of several of the interdisciplinary connections and benefits of the works to those outside of the field of art
Assessing vocational rehabilitation practices at Employment Action in Prince George
No full textNo abstract available.The original print copy of this thesis may be available here: http://wizard.unbc.ca/record=b159866
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