Screening molecular markers for prediction of recurrence and prognosis of colorectal cancer.

• Project/Area Number: 20390163
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Tohoku University
• Principal Investigator: ISHIOKA Chikashi 東北大学, 加齢医学研究所, 教授 (60241577)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Masanobu 東北大学, 病院, 助教 (00447161) ; TAKAHASHI Shin 東北大学, 病院, 助教 (20431570)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 腫瘍検査学 / 大腸癌 / 抗がん剤感受性予測 / 予後予測 / 分子マーカー / 再発予測 / 感受性予測

Research Abstract

To identify gene sets for prediction of prognosis or for prediction of efficacy of anticancer drugs in metastatic colorectal cancer (mCRC), mRNA were extracted from tumor tissues of mCRC and were analyzed for oligonucleotide microarray. We found that mCRC were clustered into 3 large clusters. Further, these clusters were correlated with KRAS status and efficacy of chemotherapy with or without anti-EGFR antibody. We are now extracting gene sets for prediction of efficacy of specific anticancer drug or regimen.

Research Products

• [Journal Article] Cur cumin analog GO-Y030 is a novel inhibitor of IKKβ that suppresses NF-κB signaling and induces apoptosis (2011)
  • Author(s): Sato A, Kudo C, Yamakoshi H, Uehara Y, Ohori H, Ishioka C, Iwabuchi Y, Shibata H
  • Journal Title: Cancer Sci Volume: 102 Pages: 1045-51
  • NAID: 10029293736
  • Peer Reviewed
• [Journal Article] Contribution of autophagic cell death to p53-dependent cell death in human glioblastoma cell line SF126 (2011)
  • Author(s): Sakamoto Y, Kato S, Takahashi M, Okada Y, Yasuda K, Watanabe G, Imai H, Sato A, Ishioka C
  • Journal Title: Cancer Sci Volume: 102 Pages: 799-807
  • NAID: 10029292419
  • Peer Reviewed
• [Journal Article] Curcumin analog GO-Y030 is a novel inhibitor of IKKβ that suppresses NF-κB signaling and induces apoptosis (2011)
  • Author(s): Sato A, et al
  • Journal Title: Cancer Sci Volume: 102 Pages: 1045-1051
  • Peer Reviewed
• [Journal Article] Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination (2010)
  • Author(s): Ransburgh, D. J., Chiba, N., Ishioka, C., Toland, A. E., Parvin, J. D
  • Journal Title: Cancer Res Volume: 70 Pages: 988-95
  • Peer Reviewed
• [Journal Article] Quality of guideline development assessed by the Evaluation Committee of the Japan Society of Clinical Oncology (2010)
  • Author(s): Shimbo T, et al
  • Journal Title: Int J Clin Oncol Volume: 15 Pages: 227-233
  • Peer Reviewed
• [Journal Article] Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination (2010)
  • Author(s): Ransburgh DJ, et al
  • Journal Title: Cancer Res Volume: 70 Pages: 988-995
  • Peer Reviewed
• [Journal Article] Structure-activity relationship of C5-curcuminoids and synthesis of their molecular probes thereof (2010)
  • Author(s): Yamakoshi H, et al
  • Journal Title: Bioorg Med Chem Volume: 18 Pages: 1083-1092
  • Peer Reviewed
• [Journal Article] Antibody-dependent cellular cytotoxicity in the immunotherapeutic mechanisms of anti-EGFR monoclonal antibody (2010)
  • Author(s): Shimodaira H, et al
  • Journal Title: Gan To Kagaku Ryoho Volume: 37 Pages: 795-798
  • Peer Reviewed
• [Journal Article] Quality of guideline development assessed by the Evaluation Committee of the Japan Society of Clinical Oncology. (2010)
  • Author(s): Shimbo T, et al.
  • Journal Title: Int J Clin Oncol (In press)
  • Peer Reviewed
• [Journal Article] Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination. (2010)
  • Author(s): Ransburgh DJ, et al.
  • Journal Title: Cancer Res 70 Pages: 988-995
  • Peer Reviewed
• [Journal Article] Structure-activity relationship of C5-curcuminoids and synthesis of their molecular probes thereof. (2010)
  • Author(s): Yamakoshi H, et al.
  • Journal Title: Bioorg Med Chem 18 Pages: 1083-1092
  • Peer Reviewed
• [Journal Article] alphaB-crystallin : A novel p53-target gene required for p53-dependent apoptosis (2009)
  • Author(s): Watanabe, G., Kato, S., Nakata, H., Ishida, T., Ohuchi, N., Ishioka, C
  • Journal Title: Cancer Sci Volume: 100 Pages: 2368-2375
  • Peer Reviewed
• [Journal Article] Newly synthesized cur cumin analog has improved potential to prevent colorectal carcinogenesis in vivo (2009)
  • Author(s): Shibata, H., Yamakoshi, H., Sato, A., Ohori, H., Kakudo, Y., Kudo, C., Takahashi, Y., Watanabe, M. , Takano, H. , Ishioka, C. , Noda, T. , Iwabuchi, Y
  • Journal Title: Cancer Sci Volume: 100 Pages: 956-60
  • NAID: 10025146044
  • Peer Reviewed
• [Journal Article] Determination of splice-site mutations in Lynch syndrome (hereditary non-polyposis colorectal cancer)patients using functional splicing assay (2009)
  • Author(s): Naruse, H., Ikawa, N., Yamaguchi, K., Nakamura, Y., Arai, M., Ishioka, C., Sugano, K., Tamura, K., Tomita, N., Matsubara, N., Yoshida, T., Moriya, Y., Furukawa, Y
  • Journal Title: Fam Cancer Volume: 8 Pages: 509-517
  • Peer Reviewed
• [Journal Article] Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer (2009)
  • Author(s): Yoshioka T, Kato S, Gamoh M, Chiba N, Suzuki T, Sakayori N, Kato S, Shibata H, Shimodaira H, Otsuka K, Kakudo Y, Takahashi S, Ishioka C
  • Journal Title: Br J Cancer Volume: 101 Pages: 1972-7
• [Journal Article] Prospective comparison of surgery alone and chemo radiotherapy with selective surgery in resectable squamous cell carcinoma of the esophagus (2009)
  • Author(s): Ariga H, Nemoto K, Miyazaki S, Yoshioka T, Ogawa Y, Sakayauchi T, Jingu K, Miyata G, Onodera K, Ichikawa H, Kamei T, Kato S, Ishioka C, Satomi S, Yamada S
  • Journal Title: Int J Radiat Oncol Biol Phys Volume: 75 Pages: 348-56
  • Peer Reviewed
• [Journal Article] Comparison of cisplatin and 5-fluorouracil chemotherapy protocols combined with concurrent radiotherapy for esophageal cancer (2009)
  • Author(s): Sakayauchi T, Nemoto K, Ishioka C, Onishi H, Yamamoto M, Kazumoto T, Makino M, Yonekura R, Itami J, Sasaki S, Suzuki G, Hayabuchi N, Tamamura H, Onimaru R, Tamamoto T, Yamada S
  • Journal Title: Jpn J Radiol Volume: 27 Pages: 131-7
  • NAID: 50007224857
  • Peer Reviewed
• [Journal Article] Phase II study of capecitabine and trastuzumab combination chemotherapy in patients with HER2 over expressing metastatic breast cancers resistant to both anthracyclines and taxanes (2009)
  • Author(s): Ishida T, Kiba T, Takeda M, Matsuyama K, Teramukai S, Ishiwata R, Masuda N, Takatsuka Y, Noguchi S, Ishioka C, Fukushima M, Ohuchi N
  • Journal Title: Cancer Chemother Pharmacol Volume: 64 Pages: 361-9
  • Peer Reviewed
• [Journal Article] Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer. (2009)
  • Author(s): Yoshioka T, et al.
  • Journal Title: Br J Cancer 101 Pages: 1972-1977
  • Peer Reviewed
• [Journal Article] Three cases of kindred with familial breast cancer in which carrier detection by BRCA gene testing was performed on family members. (2009)
  • Author(s): Nomizu T, et al.
  • Journal Title: Breast Cancer (In press)
  • Peer Reviewed
• [Journal Article] alphaB-crystallin : a novel p53-target gene required for p53-dependent a poptosis. (2009)
  • Author(s): Watanabe G, et al.
  • Journal Title: Cancer Sci 100 Pages: 2368-2375
  • Peer Reviewed
• [Journal Article] Prospective comparison of surgery alone and chemoradiotherapy with selective surgery in resectable squamous cell carcinoma of the esophagus. (2009)
  • Author(s): Ariga H, et al.
  • Journal Title: Int J Radiat Oncol Biol Phys 75 Pages: 348-356
  • Peer Reviewed
• [Journal Article] Determination of splice-site mutations in Lynch syndrome(hereditary non-polyposis colorectal cancer)patients using functional splicing assay. (2009)
  • Author(s): Naruse H, et al.
  • Journal Title: Fam Cancer 8 Pages: 509-517
  • Peer Reviewed
• [Journal Article] Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo. (2009)
  • Author(s): Shibata H, et al.
  • Journal Title: Cancer Sci 100 Pages: 956-960
  • Peer Reviewed
• [Journal Article] Comparison of cisplatin and 5-fluorouracil chemotherapy protocols combined with concurrent radiotherapy for esophageal cancer. (2009)
  • Author(s): Sakayauchi T, et al.
  • Journal Title: Jpn J Radiol 27 Pages: 131-137
  • Peer Reviewed
• [Journal Article] Phase II study of capecitabine and trastuzumab combination chemotherapy in patients with HER2 overexpressing metastatic breast cancers resistant to both anthracyclines and taxanes. (2009)
  • Author(s): Ishida T, et al.
  • Journal Title: Cancer Chemother Pharmacol 64 Pages: 361-369
  • Peer Reviewed
• [Journal Article] Rapid Recruitment of BRCA1 to DNA Double-Strand Breaks Is Dependent on Its Association with Ku80 (2008)
  • Author(s): Wei, L., Lan, L., Hong, Z., Yasui, A., Ishioka, C., Chiba, N
  • Journal Title: Mol Cell Biol Volume: 28 Pages: 7380-93
  • Peer Reviewed
• [Journal Article] Prediction of breast cancer prognosis by gene expression profile of TP53 status (2008)
  • Author(s): Takahashi, S., Moriya, T., Ishida, T., Shibata, H., Sasano, H., Ohuchi, N., Ishioka, C
  • Journal Title: Cancer Sci Volume: 99 Pages: 324-32
  • NAID: 10024002457
  • Peer Reviewed
• [Journal Article] Analysis of p53 mutation status in human cancer cell lines : a paradigm for cell line cross-contamination (2008)
  • Author(s): Berglind, H., Pawitan, Y., Kato, S., Ishioka, C., Soussi, T
  • Journal Title: Cancer Biol Ther Volume: 7 Pages: 699-708
  • Peer Reviewed
• [Journal Article] Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80 (2008)
  • Author(s): Wei, L, et.al.
  • Journal Title: Molecular Celluar Biology 28 Pages: 7380-7393
  • Peer Reviewed
• [Journal Article] Phase II study of capecitabine and trastuzumab combination chemotherapy in patients with HER2 overexpressing metastatic breast cancers resistant to both anthracyclines and taxanes (2008)
  • Author(s): Ishida, T., et.al.
  • Journal Title: Cancer Chemotherapy and Pharmacology (In press)
  • Peer Reviewed
• [Journal Article] Analysis of p53 mutation status in human cancer cell lines : a paradigm for cell line cross-contamination (2008)
  • Author(s): Berglind, H., et.al.
  • Journal Title: Cancer Biology and Therapy 7 Pages: 699-708
  • Peer Reviewed
• [Presentation] A randomized pilot study comparing safety and efficacy of irinotecan plus S-1 (IRIS)plus bevacizumab (BV)and modified (m)FOLFIRI plus BV in patients (pts)with metastatic colorectal cancer (marc): First report of T-CORE0702 (2011)
  • Author(s): Kato, S. , Andoh, H. , Gamoh, M. , Yamaguchi, T. , Murakawa, Y. , Sasaki, Y. , Takahashi, S. , Shimodaira, H. , Yoshioka, T. , Ishioka, C.
  • Organizer: 2011 Gastrointestinal Cancers Symposium
  • Place of Presentation: Florida・Orland world Center Marriott.General Poster Session C
  • Year and Date: 2011-01-22
• [Presentation] Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-refractory patients with EGFR-positive advanced and/or metastatic colorectal cancer : Evaluation of the efficacy and safety based on KRAS mutation status (T-CORE0801) (2011)
  • Author(s): Shimodaira, H. , Soeda, H. , Gamoh, M. , Andoh, H. , Yamaguchi, T. , Watanabe, M. , Isobe, H. , Sudo, T. , Kato, S. , Ishioka, C.
  • Organizer: 2011 Gastrointestinal Cancers Symposium
  • Place of Presentation: Florida・Orland world Center Marriott.General Poster Session C
  • Year and Date: 2011-01-22
• [Presentation] Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-refractory patients with EGFR-positive advanced and/or metastatic colorectal cancer : Evaluation of the efficacy and safety based on KRAS mutation status (T-CORE0801) (2011)
  • Author(s): Shimodaira H, et al
  • Organizer: 2011 Gastrointestinal Cancers Symposium (ASCO)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-01-21
• [Presentation] A randomized pilot study comparing safety and efficacy of irinotecan plus S-1 (IRIS) plus bevacizumab (BV) and modified (m) FOLFIRl plus BV in patients (pts) with metastatic colorectal cancer (mCRC) : First report of T-CORE0702 (2011)
  • Author(s): Kato S, et al
  • Organizer: 2011 Gastrointestinal Cancers Symposium (ASCO)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-01-21
• [Presentation] 進行・再発大腸癌におけるKRAS、BRAFおよびPIK3CA遺伝子変異解析とcetuximabの治療効果 (2010)
  • Author(s): 添田大司
  • Organizer: 第8回日本臨床腫瘍学会学術集会
  • Place of Presentation: 東京ビッグサイト(東京都)
  • Year and Date: 2010-03-19
• [Presentation] 進行・再発大腸癌におけるcetuximabの治療効果予測因子(KRAS、BRAFおよびPIK3CA遺伝子変異)の解析 (2010)
  • Author(s): 添田大司
  • Organizer: 第43回制癌剤適応研究会
  • Place of Presentation: 仙台・仙台市情報・産業プラザ(AER)(仙台市)
  • Year and Date: 2010-03-12
• [Presentation] がん薬物療法と分子マーカー (2009)
  • Author(s): 石岡千加史
  • Organizer: 第1回北海道臨床腫瘍研究会
  • Place of Presentation: 札幌グランドホテル(旭川市)
  • Year and Date: 2009-11-28
• [Presentation] 仮説に基づくマーカーと仮説に基づかないマーカー (2009)
  • Author(s): 石岡千加史
  • Organizer: 第47回日本癌治療学会総会シンポジウム20日本癌学会、日本癌治療学会、日本臨床腫瘍学会合同シンポジウム「がんのバイオマーカーと分子標的薬」
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-24
• [Presentation] 当科におけるGIST治療の検討 (2009)
  • Author(s): 小峰啓吾
  • Organizer: 第47回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-23
• [Presentation] 当院における進行・再発大腸癌に対するKRAS遺伝子解析の実際 (2009)
  • Author(s): 添田大司
  • Organizer: 第47回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-23
• [Presentation] 3次治療以降でセツキシマブ、イリノテカン併用療法が奏功したKRAS野生型進行直腸癌の2症例 (2009)
  • Author(s): 西條憲
  • Organizer: 第36回東北・大腸癌研究会
  • Place of Presentation: 福島ビューホテル(福島市)
  • Year and Date: 2009-09-11
• [Presentation] 大腸癌治療の分子マーカー (2009)
  • Author(s): 石岡千加史
  • Organizer: 宮城大腸癌セミナー
  • Place of Presentation: 仙台ホテルモントレ(仙台市)
  • Year and Date: 2009-08-01
• [Presentation] 治癒切除不能な進行・再発大腸癌に対しKRASおよびBRAF遺伝子変異解析を行った症例の治療成績の検討 (2009)
  • Author(s): 添田大司
  • Organizer: 第13回日本がん分子標的治療学会学術集会
  • Place of Presentation: ホテルクレメント徳島(徳島市)
  • Year and Date: 2009-06-25
• [Presentation] MSH2のintron5のsplice donor siteに変異を認めたHNPCCの一家系 (2009)
  • Author(s): 高橋雅信
  • Organizer: 第15回日本家族性腫瘍学会学術集会
  • Place of Presentation: 秋葉原コンベンションホール(東京都)
  • Year and Date: 2009-06-12
• [Presentation] Cytoplasmically localized wild-type p53 and S121F super p53 still retains apoptosis inducible abilities (2009)
  • Author(s): Yasuda, K. , Kato, S. , Sakamoto, Y. , Watanabe, G. , Kakudo, Y. , Ishioka, C
  • Organizer: 2009 AACR Annual Meeting
  • Place of Presentation: Denver Colorado USA.Poster
  • Year and Date: 2009-04-19
• [Presentation] 大腸癌薬物療法の進歩 (2008)
  • Author(s): Ishioka, C
  • Organizer: 日本の標準と国際標準の違いと将来
  • Place of Presentation: 北京・中日友好病院臨床研究所講学庁. 招聘講演
  • Year and Date: 2008-11-06
• [Presentation] A new method for classifying breast cancers by gene expression profile of TP53 status in multiplex RT-PCR (2008)
  • Author(s): Mashiko, S., et.al.
  • Organizer: 2nd JCA-AACR Special Joint Conference The Latest Advances in Breast Cancer Research
  • Place of Presentation: 兵庫県淡路島
  • Year and Date: 2008-07-15
• [Presentation] A Phase 1/2 study of sequential combination with irinotecan and S-1 in patients with metastatic colorectal cancer (2008)
  • Author(s): Yoshioka, T., et.al.
  • Organizer: 2008 ASCO Annual Meeting
  • Place of Presentation: 米国シカゴ市
  • Year and Date: 2008-06-02
• [Book] 入門腫瘍内科学(編集委員), 秋田弘俊, 石岡千加史, 田村和夫, 中川和彦, 原田実根, 南博信編入門腫瘍内科学(直腸, 結腸癌) (2009)
  • Author(s): 秋田弘俊, 石岡千加史, 田村和夫, 中川和彦, 原田実根, 南博信
  • Publisher: 篠原出版社
• [Book] がん分子標的治療薬開発におけるProof of concept日本がん分子標的治療学会, 曽根三郎, 鶴尾隆編がん分子標的治療研究実践マニュアル (2009)
  • Author(s): 石岡千加史
  • Publisher: 金芳堂
• [Patent(Industrial Property Rights)] がんの予後予測方法 (2009)
  • Inventor(s): 石岡千加史、高橋信
  • Industrial Property Rights Holder: 東北大学
  • Acquisition Date: 2009-09-11