乳がんの個性診断と分子病態解明

2009 年度 研究成果報告書

• 研究課題/領域番号: 17015027
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 大阪大学
• 研究代表者: 野口 眞三郎 大阪大学, 医学系研究科, 教授 (10303942)
• 研究分担者: 玉木 康博 大阪大学, 大学院・医学研究科, 准教授 (10273690) ; 金 昇晋 大阪大学, 大学院・医学研究科, 准教授 (90346213) ; 三好 康雄 兵庫医科大学, 医学部, 准教授 (50283784)
• 研究期間 (年度): 2005 – 2009
• キーワード: 乳癌 / 予後 / 化学療法感受性 / 遺伝子発現 / 細胞周期 / プロファイリング

研究概要

乳癌組織を用いた遺伝子発現プロファイルおよび細胞周期プロファイル解析によって、術後補助ホルモン療法を受けた乳癌患者の予後を従来の臨床病理学的因子よりもより正確に予測し得る予後の診断モデルを作成した。また、術前化学療法を実施する前に採取された腫瘍組織の遺伝子発現プロファイル解析によって、術前化学療法(タキサン→アンスラサイクリン)の効果を精度良く予測し得る化学療法感受性の診断モデルを作成した。

研究成果

• [雑誌論文] Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. (2009)
  • 著者名/発表者名: Tanei, T., Morimoto, K., Shimazu, K., Kim, S.J., Tanji, Y., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Clin Cancer Res 15 ページ: 4234-4241
  • 査読あり
• [雑誌論文] Molecular detection of lymph node metastases in breast cancer patients: Results of a multi-centric trial using a fully automated system, the one-step nucleic acid amplification (OSNA) assay. (2009)
  • 著者名/発表者名: Tamaki, Y., Akiyama, F., Iwase, T., Kaneko, K.,Tsuda, H., Sato, K., Ueda, S., Mano, M., Masuda, N., Takeda, M., Tsujimoto, M., Yoshidome, K., Inaji, H., Nakajima, H., Komoike, Y., Kataoka, T., Nakamura, S., Suzuki, K., Tsugawa, K., Wakasa, K., Okino, T., Kato, Y., Noguchi, S., Matsuura
  • 雑誌名: Clin Cancer Res 15 ページ: 2879-2884
  • 査読あり
• [雑誌論文] Genetic polymorphisms of CYP2D6*10 and CYP2C19*2, *3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen. (2009)
  • 著者名/発表者名: Okishiro, M., Taguchi, T., Jin Kim, S., Shimazu, K., Tamaki, Y., Noguchi, S.
  • 雑誌名: Cancer 115 ページ: 952-961
  • 査読あり
• [雑誌論文] Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells. (2009)
  • 著者名/発表者名: Nakayama, S., Torikoshi, Y., Takahashi, T., Yoshida, T., Sudo, T., Matsushima, T., Kawasaki, Y., Katayama, A., Gohda, K., Hortobagyi, G.N., Noguchi, S., Sakai, T., Ishihara, H., Ueno, N.T.
  • 雑誌名: Breast Cancer Res 11 ページ: R12
  • 査読あり
• [雑誌論文] Intraoperative frozen section analysis of sentinel lymph node in breast cancer patients treated with neoadjuvant chemotherapy. (2008)
  • 著者名/発表者名: Shimazu, K., Tamaki, Y., Taguchi, T., Tsukamoto, F., Kasugai, T., Noguchi, S.
  • 雑誌名: Ann Surg Oncol 15 ページ: 1717-1722
  • 査読あり
• [雑誌論文] Incidence of joint symptoms and bone fractures in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole. (2008)
  • 著者名/発表者名: Okishiro, M., Taguchi, T., Kim, S.J., Tanji, Y., Shimazu, K., Tamaki, Y., Noguchi, S.
  • 雑誌名: J Cancer Res Clin Oncol 135 ページ: 823-827
  • 査読あり
• [雑誌論文] Connexin26 expression is associated with aggressive phenotype in human papillary and follicular thyroid cancers. (2008)
  • 著者名/発表者名: Naoi, Y., Miyoshi, Y., Taguchi, T., Kim, S.J., Arai, T., Maruyama, N., Tamaki, Y., Noguchi, S.
  • 雑誌名: Cancer Lett 262 ページ: 248-256
  • 査読あり
• [雑誌論文] Growth-inhibitory effect of adiponectin via adiponectin receptor 1 on human breast cancer cells through inhibition of S-phase entry without inducing apoptosis. (2008)
  • 著者名/発表者名: Nakayama, S., Miyoshi, Y., Ishihara, H., Noguchi, S.
  • 雑誌名: Breast Cancer Res Treat 112 ページ: 405-410
  • 査読あり
• [雑誌論文] Low nuclear grade but not cell proliferation predictive of pathological complete response to docetaxel in human breast cancers. (2008)
  • 著者名/発表者名: Miyoshi, Y., Kurosumi, M., Kurebayashi, J., Matsuura, N., Takahashi, M., Tokunaga, E., Egawa, C., Masuda, N., Kim, S.J., Okishiro, M., Yanagisawa, T., Ueda, S., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: J Cancer Res Clin Oncol 134 ページ: 561-567
  • 査読あり
• [雑誌論文] Topoisomerase IIalpha-positive and BRCA1-negative phenotype: Association with favorable response to epirubicin-based regimens for human breast cancers. (2008)
  • 著者名/発表者名: Miyoshi, Y., Kurosumi, M., Kurebayashi, J., Matsuura, N., Takahashi, M., Tokunaga, E., Egawa, C., Masuda, N., Kim, S.J., Okishiro, M., Yanagisawa, T., Ueda, S., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Cancer Lett 26 ページ: 44-53
  • 査読あり
• [雑誌論文] Quantitative assessment of mammographic density and breast cancer risk for Japanese women. (2008)
  • 著者名/発表者名: Kotsuma, Y., Tamaki, Y., Nishimura, T., Tsubai, M., Ueda, S., Shimazu, K., Jin Kim, S., Miyoshi, Y., Tanji, Y., Taguchi, T., Noguchi, S.
  • 雑誌名: Breast 17 ページ: 27-35
  • 査読あり
• [雑誌論文] Determination of the specific activity of CDK1 and CDK2 as a novel prognostic indicator for early breast cancer. (2008)
  • 著者名/発表者名: Kim, S.J., Nakayama, S., Miyoshi, Y., Taguchi, T., Tamaki, Y., Matsushima, T., Torikoshi, Y., Tanaka, S., Yoshida, T., Ishihara, H., Noguchi, S.
  • 雑誌名: Ann Oncol 19 ページ: 68-72
  • 査読あり
• [雑誌論文] Association of GSTP1 expression with resistance to docetaxel and paclitaxel in human breast cancers. (2008)
  • 著者名/発表者名: Arai, T., Miyoshi, Y., Kim, S.J., Akazawa, K., Maruyama, N., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Eur J Surg Oncol 34 ページ: 734-738
  • 査読あり
• [雑誌論文] Potential of reduction in total tumor volume measured with 3D-MRI as a prognostic factor for locally-advanced breast cancer patients treated with primary chemotherapy. (2008)
  • 著者名/発表者名: Akazawa, K., Tamaki, Y., Taguchi, T., Tanji, Y., Miyoshi, Y., Kim, S.J., Shimazu, K., Ueda, S., Yanagisawa, T., Okishiro, N., Imazato, M., Yasuyuki, K., Sato, Y., Tamura, S., Noguchi, S.
  • 雑誌名: Breast J 14 ページ: 523-531
  • 査読あり
• [雑誌論文] One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. (2007)
  • 著者名/発表者名: Tsujimoto, M., Nakabayashi, K., Yoshidome, K., Kaneko, T., Iwase, T., Akiyama, F., Kato, Y., Tsuda, H., Ueda, S., Sato, K., Tamaki, Y., Noguchi, S., Kataoka, T. R., Nakajima, H., Komoike, Y., Inaji, H., Tsugawa, K., Suzuki, K., Nakamura, S., Daitoh, M., Otomo, Y., Matsuura, N.
  • 雑誌名: Clin Cancer Res 13 ページ: 4807-4816
  • 査読あり
• [雑誌論文] Demonstration of Adiponectin Receptors 1 and 2 mRNA expression in human breast cancer cells. (2007)
  • 著者名/発表者名: Takahata, C., Miyoshi, Y., Irahara, N., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Cancer Lett 250 ページ: 229-236
  • 査読あり
• [雑誌論文] Low LATS2 mRNA level can predict favorable response to epirubicin plus cyclophosphamide, but not to docetaxel, in breast cancers. (2007)
  • 著者名/発表者名: Takahashi, Y., Miyoshi, Y., Morimoto, K., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: J Cancer Res Clin Oncol 133 ページ: 501-519
  • 査読あり
• [雑誌論文] Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers. (2007)
  • 著者名/発表者名: Ooe, A., Kato, K., Noguchi, S.
  • 雑誌名: Breast Cancer Res Treat 101 ページ: 305-315
  • 査読あり
• [雑誌論文] Connexin26 expression is associated with lymphatic vessel invasion and poor prognosis in human breast cancer. (2007)
  • 著者名/発表者名: Naoi, Y., Miyoshi, Y., Taguchi, T., Kim, S.J., Arai, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Breast Cancer Res Treat 106 ページ: 11-17
  • 査読あり
• [雑誌論文] Clinicopathologic Analysis of Breast Cancers with PIK3CA Mutations in Japanese Women. (2007)
  • 著者名/発表者名: Maruyama, N., Miyoshi, Y., Taguchi, T., Tamaki, Y., Monden, M., Noguchi, S.
  • 雑誌名: Clin Cancer Res 13 ページ: 408-414
  • 査読あり
• [雑誌論文] Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells. (2007)
  • 著者名/発表者名: Kagara, N., Tanaka, N., Noguchi, S., Hirano, T.
  • 雑誌名: Cancer Sci 98 ページ: 692-697
  • 査読あり
• [雑誌論文] A multi-class predictor based on a probabilistic model: application to gene expression profiling-based diagnosis of thyroid tumors. (2006)
  • 著者名/発表者名: Yukinawa, N., Oba, S., Kato, K., Taniguchi, K., Iwao-Koizumi, K., Tamaki, Y., Noguchi, S., Ishii, S.
  • 雑誌名: BMC Genomics 7 ページ: 190
  • 査読あり
• [雑誌論文] High expression of ubiquitin carboxy-terminal hydrolase-L1 and -L3 mRNA predicts early recurrence in patients with invasive breast cancer. (2006)
  • 著者名/発表者名: Miyoshi, Y., Nakayama, S., Torikoshi, Y., Tanaka, S., Ishihara, H., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Cancer Sci 97 ページ: 523-529
  • 査読あり
• [雑誌論文] High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels. (2006)
  • 著者名/発表者名: Miyoshi, Y., Funahashi, T., Tanaka, S., Taguchi, T., Tamaki, Y., Shimomura, I., Noguchi, S.
  • 雑誌名: Int J Cancer 118 ページ: 1414-1419
  • 査読あり
• [雑誌論文] Quantitative analysis of aromatase, sulfatase and 17beta-HSD(1) mRNA expression in soft tissue metastases of breast cancer. (2006)
  • 著者名/発表者名: Irahara, N., Miyoshi, Y., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Cancer Lett 243 ページ: 23-31
  • 査読あり
• [雑誌論文] Quantitative analysis of aromatase mRNA expression derived from various promoters (I. 4, I. 3, PII and I. 7) and its association with expression of TNF-alpha, IL-6 and COX-2 mRNAs in human breast cancer. (2006)
  • 著者名/発表者名: Irahara, N., Miyoshi, Y., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Int J Cancer 118 ページ: 1915-1921
  • 査読あり
• [雑誌論文] Association of GSTP1 CpG Islands Hypermethylation with Poor Prognosis in Human Breast Cancers. (2006)
  • 著者名/発表者名: Arai, T., Miyoshi, Y., Kim, S.J., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Breast Cancer Res Treat 100 ページ: 169-176
  • 査読あり
• [雑誌論文] Preoperative evaluation of residual tumor extent by three-dimensional magnetic resonance imaging in breast cancer patients treated with neoadjuvant chemotherapy. (2006)
  • 著者名/発表者名: Akazawa, K., Tamaki, Y., Taguchi, T., Tanji, Y., Miyoshi, Y., Kim, S.J., Ueda, S., Yanagisawa, T., Sato, Y., Tamura, S., Noguchi, S.
  • 雑誌名: Breast J 12 ページ: 130-137
  • 査読あり
• [雑誌論文] Differentiation of follicular thyroid adenoma from carcinoma by means of gene expression profiling with adapter-tagged competitive polymerase chain reaction. (2005)
  • 著者名/発表者名: Taniguchi, K., Takano, T., Miyauchi, A., Koizumi, K., Ito, Y., Takamura, Y., Ishitobi, M., Miyoshi, Y., Taguchi, T., Tamaki, Y., Kato, K., Noguchi, S.
  • 雑誌名: Oncology 69 ページ: 428-435
  • 査読あり
• [雑誌論文] Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. (2005)
  • 著者名/発表者名: Takahashi, Y., Miyoshi, Y., Takahata, C., Irahara, N., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 雑誌名: Clin Cancer Res 11 ページ: 1380-1385
  • 査読あり
• [雑誌論文] Postoperative adjuvant therapy with tamoxifen, tegafur plus uracil, or both in women with node-negative breast cancer: a pooled analysis of six randomized controlled trials. (2005)
  • 著者名/発表者名: Noguchi, S., Koyama, H., Uchino, J., Abe, R., Miura, S., Sugimachi, K., Akazawa, K., Abe, O.
  • 雑誌名: J Clin Oncol 23 ページ: 2172-2184
  • 査読あり
• [雑誌論文] Prediction of Response to Docetaxel by Immunohistochemical Analysis of CYP3A4 Expression in Human Breast Cancers. (2005)
  • 著者名/発表者名: Miyoshi, Y., Taguchi, T., Kim, S.J., Tamaki, Y., Noguchi, S.
  • 雑誌名: Breast Cancer 12 ページ: 11-15
  • 査読あり
• [雑誌論文] High thioredoxin expression is associated with resistance to docetaxel in primary breast cancer. (2005)
  • 著者名/発表者名: Kim, S.J., Miyoshi, Y., Taguchi, T., Tamaki, Y., Nakamura, H., Yodoi, J., Kato, K., Noguchi, S.
  • 雑誌名: Clin Cancer Res 11 ページ: 8425-8430
  • 査読あり
• [雑誌論文] Cancer gene expression database (CGED): a database for gene expression profiling with accompanying clinical information of human cancer tissues. (2005)
  • 著者名/発表者名: Kato, K., Yamashita, R., Matoba, R., Monden, M., Noguchi, S., Takagi, T., Nakai, K.
  • 雑誌名: Nucleic Acids Res 33 ページ: D533-536
  • 査読あり
• [雑誌論文] Prediction of docetaxel response in human breast cancer by gene expression profiling. (2005)
  • 著者名/発表者名: Iwao-Koizumi, K., Matoba, R., Ueno, N., Kim, S.J., Ando, A., Miyoshi, Y., Maeda, E., Noguchi, S., Kato, K.
  • 雑誌名: J Clin Oncol 23 ページ: 422-431
  • 査読あり
• [雑誌論文] Possible involvement of aromatase overexpression induced by cyclo-oxygenase-2 in the pathogenesis of idiopathic gynecomastia. (2005)
  • 著者名/発表者名: Irahara, N., Miyoshi, Y., Taguchi, T., Tamaki, Y., Noguchi, S., Harada, N.
  • 雑誌名: Endocr Res 31 ページ: 219-227
  • 査読あり
• [学会発表] Breast cancer stem cells identified by ALDH1 expression were associated with resistance to sequential paclitaxel and epirubicin-based chemotherapy for human breast cancers. (2009)
  • 著者名/発表者名: Tanei, T., Morimoto, K., Shimazu, K., Kim, S.J., Tanji, Y., Taguchi, T., Tamaki, Y., Noguchi, S.
  • 学会等名: 32nd San Antonio Breast Cancer Symposium
  • 発表場所: San Antonio TX, U.S.A.
  • 年月日: 2009-12-11
• [学会発表] Ratio of cyclin-dependent kinase 1 (CDK1) activity to CDK2 activity after ex vivo paclitaxel treatment predicts response to paclitaxel in human breast cancer. (2008)
  • 著者名/発表者名: Kim, S.J., Ishihara, H., Noguchi, S.
  • 学会等名: 31st Annual San Antonio Breast Cancer Symposium
  • 発表場所: San Antonio TX, U.S.A.
  • 年月日: 2008-12-12
• [学会発表] Cyclin-dependent kinase 2 to 1 specific activity ratio predicts response to epirubicin and paclitaxel in human breast cancer. (2007)
  • 著者名/発表者名: Kim, S.J., Ishihara, H., Noguchi, S.
  • 学会等名: 30th Annual San Antonio Breast Cancer Symposium
  • 発表場所: San Antonio TX, U.S.A.
  • 年月日: 2007-12-14