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学位論文 |
学位
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田中, 慎吾 ; Tanaka, Shingo
概要:
博士論文要旨Abstract 要約Outline 以下に掲載：Journal of Neuro-Oncology 121(2) pp.239-250 2015. Springer. 共著者：Shingo Tanaka, Mitsutoshi
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Nakada, Daisuke Yamada, Ichiro Nakano, Tomoki Todo, Yasushi Ino, Takayuki Hoshii, Yuko Tadokoro, Kumiko Ohta, Mohamed A.E. Ali, Yutaka Hayashi, Jun-ichiro Hamada, Atsushi Hirao
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| 2.
論文 |
論文
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Kinoshita, Masashi ; Nakada, Mitsutoshi ; Tanaka, Shingo ; Ozaki, Noriyuki ; Hamada, Jun-ichiro ; Hayashi, Yutaka
概要:
金沢大学医薬保健研究域医学系<br />Background: The retrochiasmatic region is one of the most challenging areas to surgically expose. Th
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e authors evaluated the transcrusal approach, which involves removal of the superior and posterior semicircular canal from the ampulla to the common crus, to expose the retrochiasmatic region and compared it with the retrolabyrinthine approach, both of which are a variation of the posterior petrosal approach with hearing preservation, with a special emphasis on the influence of temporal lobe retraction. Methods: Six sides of silicone-injected cadaveric heads were dissected using two approaches: the transcrusal approach and the retrolabyrinthine approach. For each craniotomy, 3 exposure parameters in the retrochiasmatic region were measured: (1) horizontal distance, (2) vertical distance, and (3) triangular area of exposure, at three different levels of temporal lobe retractions: 0, 5, and 10 mm of retraction from the level of the tentorial incisura. Results: Without temporal lobe retraction, only the transcrusal and not the retrolabyrinthine approach provided a direct exposure of the retrochiasmatic region, especially in the horizontal distance (p < 0.001). At all levels of temporal lobe retraction, the transcrusal approach provided greater exposure in the horizontal and vertical distances and in the area of exposure. Nonetheless, in the horizontal distance, the difference between the transcrusal and retrolabyrinthine approaches decreased along with increased temporal lobe retraction, and almost no difference was obtained at 10 mm of retraction. Conclusions: Posterior petrosal approaches can provide an excellent exposure of the retrochiasmatic region. Of these two approaches, namely, transcrusal and retrolabyrinthine with hearing preservation, the transcrusal approach offers greater exposure than the retrolabyrinthine approach. The beneficial effect of partial labyrinthectomy of the transcrusal approach to the retrochiasmatic region is accentuated in the exposure of the horizontal distance with less temporal lobe retraction. © 2010 Springer-Verlag.
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論文 |
論文
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Kinoshita, Hideki ; Tanaka, Shingo ; Nishimori, Natsu ; Dejima, Hiroshi ; Inomata, Katsuhiko
概要:
2-Hydroxymethyl-1-methylsulfonyl-3,4-disubstituted pyrroles and 2-hydroxymethyl-3,4-disubstituted pyrroles were effectively converted into the corresponding 2-(substituted methyl)pyrrole derivatives by the reaction with
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various nucleophiles in the presence of base. These products were further transformed to the corresponding porphyrins regioselectively under almost neutral or basic conditions.
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| 4.
論文 |
論文
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田中, 慎吾 ; Tanaka, Shingo
概要:
金沢大学医薬保健研究域医学系<br />膠芽腫は予後不良な悪性腫瘍であり、膠芽腫幹細胞に対する治療が再発予防や根治性の向上に重要とされている。我々は、Notch阻害薬はAktシグナル抑制によって膠芽腫幹細胞へ効果を示すことと高感受性群と低感
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受性群に分けられることを報告した。本研究では、Notch阻害剤低感受性膠芽腫幹細胞群に対しNotch阻害剤とAkt阻害剤の併用療法の有効性を評価した。2剤併用療法は単剤よりも有意に細胞増殖抑制、幹細胞形質維持の抑制、アポトーシス誘導の増強を認めた。したがってNotch阻害薬にAkt阻害薬を併用することによりNotch阻害剤低感受性膠芽腫幹細胞を制御できることは示唆された。<br />Glioblastoma is the most malignant primary brain tumor in humans. The patinets with glioblastoma have a uniformly poor prognosis. The significance of targeting glioblastoma-stem cells may be important for successful treatment. In this study, we analyzed the efficacy of the Nothc inhibitor and Akt inhibitor for glioblastoma stem cell with Notch inhibitor resistance. Notch inhibitor concomitant Akt inhibitor treatment enhanced the effect by monothearapy such as suppression of cell proliferation and stemness maintenance, and promotion of apoptosis.<br />研究課題/領域番号:15K19956, 研究期間(年度):2015-04-01 - 2017-03-31
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| 5.
論文 |
論文
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田中, 慎吾 ; Tanaka, Shingo
概要:
膠芽腫は予後不良な悪性脳腫瘍であり、膠芽腫幹細胞に対する治療が再発予防や根治性の向上に重要とされている。本研究では、9種類の膠芽腫患者由来膠芽腫幹細胞に対しNotch阻害剤MRK-003の有効性を評価した。MRK-003は全ての膠芽腫幹細胞
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に対し、細胞増殖抑制、アポトーシス促進、幹細胞形質抑制の効果を示した。使用した膠芽腫幹細胞は高感受性群と低感受性群に分けられた。IC50(50%阻害濃度）はCD44の発現量と負の相関関係、CD133の発現量と正の相関関係を認めた。MRK-003はCD44高値、CD133低値の膠芽腫幹細胞に有効であることが示唆された。<br />Glioblastoma is the most malignant primary brain tumor in humans. The patients with glioblastoma have a uniformly poor prognosis. The significance of targeting glioblastoma-initiating cells (GICs) may be important for successful treatment of glioblastoma. In this study, we analyzed the effect of the Notch inhibitor MRK-003 on nine patient-derived GICs. MRK-003 suppressed GIC's proliferation and stemness maintenance, and promoted their apoptosis. Based on their sensitivities to MRK-003, the nine GICs were divided into “relatively sensitive” and “relatively resistant” GICs. The IC50(half maximal inhibitory concentration) of MRK003 in a set of GICs exhibited a negative correlation with CD44 and positive correlation with CD133. Our study suggested that MRK-003 may exhibit significant therapeutic potential for GICs with CD44-high and CD133-low expression.<br />研究課題/領域番号:25861263, 研究期間(年度):2013-04-01 - 2015-03-31
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| 6.
論文 |
論文
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田中, 慎吾 ; Tanaka, Shingo
概要:
金沢大学医薬保健研究域医学系<br />膠芽腫は原発性悪性脳腫瘍であり予後不良な難治性の疾患である。本研究は膠芽腫幹細胞に対する標的治療研究である。我々はNotchシグナルの活性指標となる核内転写因子RBPJに着目した。膠芽腫組織ではRBP
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Jの発現が正常脳より高いこと、膠芽腫幹細胞は分化型膠芽腫細胞よりもRBPJの発現が高いことを確認した。膠芽腫幹細胞のRBPJ抑制により細胞増殖低下、幹細胞形質喪失を認めた。メカニズムとしてRBPJの阻害により下流因子のインターロイキン6とSTATシグナルの抑制が誘導されたこと突き止めた。動物実験においても腫瘍の縮小を認めた。膠芽腫幹細胞制御にはRBPJの阻害が有効であると示唆された。<br />Glioblastoma is a primary malignant brain tumor and is an intractable disease with a poor prognosis. This study is a targeted therapeutic study against glioblastoma stem cells. We focused on the nuclear transcription factor RBPJ, which is an active indicator of Notch signaling. RBPJ expression was higher in glioblastoma tissue than in normal brain, and glioblastoma stem cells had higher RBPJ expression than differentiated glioblastoma cells. RBPJ inhibition of glioblastoma stem cells results in decreased cell proliferation and loss of stem cell phenotype. As a mechanism, we found that inhibition of RBPJ induced inhibition of the downstream factors interleukin 6 and STAT signal. Tumor reduction was also checked in animal studies. It suggested that inhibition of RBPJ is effective for the regulation of glioblastoma stem cells.<br />研究課題/領域番号:17K10858, 研究期間(年度):2017-04-01 - 2020-03-31<br />出典：「Notchシグナルの核内転写因子RBP-Jk抑制によるグリオーマ幹細胞の制御」研究成果報告書 課題番号17K10858（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-17K10858/17K10858seika/)を加工して作成
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