2003 年度実績報告書

薬剤感受性と血管新生の分子標的から見たがんの診断と治療

研究課題

研究課題/領域番号	12217105
研究機関	久留米大学
研究代表者	桑野信彦久留米大学, 医学部, 教授 (80037431)
キーワード	薬剤感受性 / 血管新生 / 分子標的治療 / 個別化治療 / ABCトランスポーター / YB-1 / トランスレーショナルリサーチ
研究概要	ABCトランスポーターとYB-1に関して構造ならびに生物活性を解析しがんにおける個別化治療に貢献する。と同時に、がんの血管新生の機序と関連する新しい分子標的を提示しがんの診断・治療へ寄与する。その結果、本年度は 1.ABCトランスポーターのうちMPR4がメトトレキセートの細胞外排出へ関与すること、ならびにMRP1とMRP2の、ロイコトリエンC4や抗がん剤の認識部位を明らかにした。と同時に、MDR1遺伝子発現に影響を及ぼす5'制御領域の遺伝子多型を見出した。 2.YB-1の核内局在がABCトランスポーターのうちMDR1(P-蛋白質)の発現に幾つかのヒトがんで特異的に関連した。さらに、YB-1による翻訳制御にいて新しい知見を発表した。 3.炎症性サイトカインTNFαやIL1βによる血管新生においてマクロファージなどの関与が重要であること、さらに、α4インテグリンやシクロオキシゲーゼ2が直接的に血管新生をスィッチすることを提示した。 4.ヒト腎がん細胞において分化や転移と関連するCap43/NDRG1遺伝子の発現がVHLによってその発現が制御されることを見出した。

研究成果
(16件)

すべてその他

すべて文献書誌 (16件)

[文献書誌] Hisaeda, K.: "IL-1β represses multidrug resistance protein2 gene expression through inactivation of IRF3 in HepG2 cells."Hepatology. (in press). (2004)
[文献書誌] Shibahara, K.: "Targeted disruption of one allele of the Y-box binding-1 (YB-1) gene in mouse embryonic stem cell and increased sensitivity to isplatin and mitomycin C."Cancer Science. (in press). (2004)
[文献書誌] Ono, M.: "Sensitivity to gefitinib (Iressa : ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the EGF receptor/ERK1/2 and EGF receptor/AKT pathway for proliferation."Molecular Cancer Therapeutics. (in press). (2004)
[文献書誌] Kuwano, T.: "Cyclooxygenase 2 is a key enzyme for inflammatory cytokinase-induced angiogenesis."The FASEB Journal. 18. 300-310 (2004)
[文献書誌] Fukuda, T.: "Characterization of 5'-untranslated region of YB-1 mRNA and autoregulation of translation by YB-1 protein."Nucleic Acid Research. 32. 611-622 (2004)
[文献書誌] Taniguchi, S.: "Genetic polymorphism at 5' regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon."Molecular Cancer Therapeutics. 2. 1351-1359 (2003)
[文献書誌] Wakisaka, Y.: "Cellular distribution of NDRG1 protein in the rat kidney and brain during normal postnatal development."The Journal of Histochemistry & Cytochemistry. 51. 1515-1525 (2003)
[文献書誌] Mochida, Y.: "The role of P-glycoprotein in intestinal tumorigenesis : disruption of mdrla suppresses polyp formation in Apc^<Min/+> mice."Carcinogenesis. 24. 1219-1224 (2003)
[文献書誌] Kohno, K.: "The pleiotropic functions of the Y-box-binding protein, YB-1."Bio Essays. 25. 691-698 (2003)
[文献書誌] Saji, H.: "Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma."Cancer Letters. 190. 191-197 (2003)
[文献書誌] Konno, T.: "Identification of domains participating in the substrate specificity and subcellular localization of the multidrug resistance proteins MRP1 and MRP2."The Journal of Biological Chemistry. 278. 22908-22917 (2003)
[文献書誌] Oda, Y.: "Nuclear expression of Y-box-binding protein-I correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma."Journal of Pathology. 199. 251-258 (2003)
[文献書誌] Masuda, K.: "Downregulation of CAP43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells."International Journal of Cancer. 105. 803-810 (2003)
[文献書誌] Nakao, S.: "Synergistic effect of TNF-α in soluble VCAM-1-induced angiogenesis through α_4 integrins."The Journal of Immunology. 170. 5704-5711 (2003)
[文献書誌] Kuwano, M.: "The basic and clinical implications of ABC transporters, Y-box-binding protein-1(YB-1)and angiogenesis-related factors in human malignancies."Cancer Science. 94. 9-14 (2003)
[文献書誌] 三島麻衣: "消化器がんの化学療法2004"日本メディカルセンター(印刷中). (2004)

2003 年度 実績報告書

薬剤感受性と血管新生の分子標的から見たがんの診断と治療

研究代表者

桑野 信彦 久留米大学, 医学部, 教授 (80037431)

研究成果

[文献書誌] Hisaeda, K.: "IL-1β represses multidrug resistance protein2 gene expression through inactivation of IRF3 in HepG2 cells."Hepatology. (in press). (2004)

[文献書誌] Shibahara, K.: "Targeted disruption of one allele of the Y-box binding-1 (YB-1) gene in mouse embryonic stem cell and increased sensitivity to isplatin and mitomycin C."Cancer Science. (in press). (2004)

[文献書誌] Ono, M.: "Sensitivity to gefitinib (Iressa : ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the EGF receptor/ERK1/2 and EGF receptor/AKT pathway for proliferation."Molecular Cancer Therapeutics. (in press). (2004)

[文献書誌] Kuwano, T.: "Cyclooxygenase 2 is a key enzyme for inflammatory cytokinase-induced angiogenesis."The FASEB Journal. 18. 300-310 (2004)

[文献書誌] Fukuda, T.: "Characterization of 5'-untranslated region of YB-1 mRNA and autoregulation of translation by YB-1 protein."Nucleic Acid Research. 32. 611-622 (2004)

[文献書誌] Taniguchi, S.: "Genetic polymorphism at 5' regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon."Molecular Cancer Therapeutics. 2. 1351-1359 (2003)

[文献書誌] Wakisaka, Y.: "Cellular distribution of NDRG1 protein in the rat kidney and brain during normal postnatal development."The Journal of Histochemistry & Cytochemistry. 51. 1515-1525 (2003)

[文献書誌] Mochida, Y.: "The role of P-glycoprotein in intestinal tumorigenesis : disruption of mdrla suppresses polyp formation in Apc^<Min/+> mice."Carcinogenesis. 24. 1219-1224 (2003)

[文献書誌] Kohno, K.: "The pleiotropic functions of the Y-box-binding protein, YB-1."Bio Essays. 25. 691-698 (2003)

[文献書誌] Saji, H.: "Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma."Cancer Letters. 190. 191-197 (2003)

[文献書誌] Konno, T.: "Identification of domains participating in the substrate specificity and subcellular localization of the multidrug resistance proteins MRP1 and MRP2."The Journal of Biological Chemistry. 278. 22908-22917 (2003)

[文献書誌] Oda, Y.: "Nuclear expression of Y-box-binding protein-I correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma."Journal of Pathology. 199. 251-258 (2003)

[文献書誌] Masuda, K.: "Downregulation of CAP43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells."International Journal of Cancer. 105. 803-810 (2003)

[文献書誌] Nakao, S.: "Synergistic effect of TNF-α in soluble VCAM-1-induced angiogenesis through α_4 integrins."The Journal of Immunology. 170. 5704-5711 (2003)

[文献書誌] Kuwano, M.: "The basic and clinical implications of ABC transporters, Y-box-binding protein-1(YB-1)and angiogenesis-related factors in human malignancies."Cancer Science. 94. 9-14 (2003)

[文献書誌] 三島 麻衣: "消化器がんの化学療法2004"日本メディカルセンター(印刷中). (2004)

2003 年度実績報告書

桑野信彦久留米大学, 医学部, 教授 (80037431)

[文献書誌] 三島麻衣: "消化器がんの化学療法2004"日本メディカルセンター(印刷中). (2004)