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2006 Fiscal Year Final Research Report Summary

Novel chmosensitivity testing using molecular dynamics responding to anticancer drugs

Research Project

Project/Area Number 17591435
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKEIO UNIVERSITY

Principal Investigator

KUBOTA Tetsuro  Keio University, School of Medicine, Professor, 医学部, 教授 (00118944)

Project Period (FY) 2005 – 2006
Keywordschemosensitivity test / cisplatin / 5-fluorouracil / gadd153 / p21 / c-jun
Research Abstract

Purpose : To evaluate whether changes in the expression of early-response genes (GADD153, p21, and c-Jun) can indicate chemotherapy response in gastric cancer.
Experimental Design : Three human gastric cancer cell lines (TMK-1,MKN-45, and MKN-74) were exposed to 5-fluorouracil (5-FU) or cisplatin (CDDP) in vitro. Xenografts of TMK-1 in nude mice were also treated with 5-FU or CDDP in vivo. For each of these treatments, we tested for a correlation between early gene expression levels and inhibition ratios (IR) derived at a later time. Finally, S-1 and CDDP were administered to 12 patients with advanced gastric cancer for three weeks. Among patients in different response groups, expression levels of GADD153, p21, and c-Jun were compared using biopsy specimens that were obtained by endoscopy soon after initiation of chemotherapy.
Results : There was a significant correlation between the expression levels of these genes at 24 hours (as measured by real-time PCR) and IRs at 72 hours in vitro … More (GADD153;r=0.89, P<0.001, p21;r=0.93, P<0.001, and c-Jun; r=0.80, P<0.001). Receiver-operating characteristic (ROC) curves revealed that the cut-off values (calculated to predict the effectiveness of chemotherapy) for GADD153, p21, and c-Jun were 1.3, 1.8, and 2.1, respectively. There was also a significant correlation between gene expression levels at 2 days and IRs at 21 days in vivo (GADD153;r = 0.77, P<0.001, p21;r = 0.85, P<0.001, and c-Jun ; r = 0.87, P<0.001). ROC curves defined the cut-off values as 1.8 for GADD153, 1.9 for p21, and 2.2 for c-Jun. In clinical Gene Expression and Response Prediction studies, levels of early-response gene expressions at 3-7 days in patients showing progressive disease (PD) were significant lower than those in patients with partial response (PR) (GADD153;P=0.002, P21;P = 0.003, and c-Jun ; P=0.033).
Conclusions : These results suggest that changes in the expression of the three early response genes soon after drug administration could improve predictions of the final outcome of chemotherapy in gastric cancer. Less

  • Research Products

    (16 results)

All 2006 2005

All Journal Article (15 results) Book (1 results)

  • [Journal Article] Gastrointestinal stromal tumor (GIST) and imatinib.2006

    • Author(s)
      Kubota T, et al.
    • Journal Title

      Int. J. Clin. Oncol. 11

      Pages: 184-189

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chemosensitivity and resistance testing : to be "standard" or to be individualized, that is the question.2006

    • Author(s)
      Kubota T, et al.
    • Journal Title

      Gastric Cancer 9

      Pages: 82-87

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Erythrocytes with T-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction.2006

    • Author(s)
      Suganuma, K, Kubota T, et al.
    • Journal Title

      Antioxid. Redox Signal. 8

      Pages: 1847-1855

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Endoscopic classifications as diagnostic factors of peptic ulcer and early gastric cancer - a possible reason why Helicobacter pylori infection causes gastric ulcers along lesser curvature.2006

    • Author(s)
      Yoshida, M., Kubota, T., et al.
    • Journal Title

      Aliment. Pharmacol. Ther. symp 2

      Pages: 303-310

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chemosensitivity and resistance testing : to be "standard" or to be individualized, that is the question.2006

    • Author(s)
      Kubota, T., Weisenthal, L.
    • Journal Title

      Gastric Cancer 9

      Pages: 82-87

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Gastrointestinal stromal tumor (GIST) and imatinib.2006

    • Author(s)
      Kubota, T.
    • Journal Title

      Int.J.Clin.Oncol. 11

      Pages: 184-189

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Erythrocytes with T-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction.2006

    • Author(s)
      Suganuma, K., Tsukada, K., Kashiba, M., Tsuneshige, A., Furukawa, T., Kubota, T., Goda, N., Kitajima, M., Yonetani, T., Suematsu, M.
    • Journal Title

      Antioxid.Redox Signal. 8(9)

      Pages: 1847-1855

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Endoscopic classifications as diagnostic factors of peptic ulcer and early gastric cancer-a possible reason why Helicobacter pylori infection causes gastric ulcers along lesser curvature.2006

    • Author(s)
      Yoshida, M., Saikawa, Y., Hosoda, S., Kumai, K., Kubota.T., Ishikawa, H., Nakamura, T., Nakamura R., Kameyama, K., Takahashi, S., Kurihara, N., Kitajima, M.
    • Journal Title

      Aliment.Pharmacol.Ther.symp 2

      Pages: 303-310

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Twelve years' progress in surgery for perforated gastric and duodenal ulcers : a retrospective study of indications for laparoscopic surgery, post-operateive course and the influence of Candida infection.2006

    • Author(s)
      Nakamura, T., Yoshida, M., Otani, Y., Kameyama, K., Ishikawa, H., Kumai, K., Kubota, T., Saikawa, Y., Kitajima, M.
    • Journal Title

      Aliment.Pharmacol.Ther.symp ser2

      Pages: 297-302

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tyrosine kinase inhibitor SU6666 inhibits peritoneal dissemination of gastric cancer via suppression of tumor angiogenesis.2005

    • Author(s)
      Tokuyama, J, Kubota T, et al.
    • Journal Title

      Anticancer Research 25

      Pages: 17-22

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis.2005

    • Author(s)
      Yozrozuya, K, Kubota T, et al.
    • Journal Title

      Oncology Report 14

      Pages: 677-682

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Tyrosine kinase inhibitor SU6666 inhibits peritoneal dissemination of gastric cancer via suppression of tumor angiogenesis.2005

    • Author(s)
      Tokuyama, J., Kubota, T., Saikawa, Y., Yoshida, M., Furukawa, T., Otani, Y., Kumai, K., Kitajima, M.
    • Journal Title

      Anticancer Research 25

      Pages: 17-22

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Gastric cancer mimicking submucosal tumor diagnosed by laparoscopic biopsy.2005

    • Author(s)
      Takahashi, T., Otani, Y., Yoshida, M., Furukawa, T., Kameyama, K., Akiba, Y., Saikawa, Y., Kubota, T., Kumai, K., Kuramochi, S., Mukai, M., Ishii, H., Kitajima, M.
    • Journal Title

      J.Laparoscopic & Advanced Surgical Techniques. 15(1)

      Pages: 51-56

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Minimally invasive surgery for gastric cancer-toward confluence of two major streams : review.2005

    • Author(s)
      Kitagawa, Y., Kitano, S., Kubota, T., Kumai, K., Otani, Y., Saikawa, Y., Yoshida, M., Kitajima, M.
    • Journal Title

      Gastric Cancer 8

      Pages: 103-110

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis.2005

    • Author(s)
      Yozrozuya, K., Kubota, T., Watanabe, M., Hasegawa, H., Ozawa, S., Kitajima, M., Chikahisa, L.M., Yamada, Y.
    • Journal Title

      Oncology Report 14

      Pages: 677-682

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Chemosensitivity volume 2 In vivo models imaging, and molecular regulators Blumenthal R. D.、 pp., : Real timeRT-PCR (Taqman^【○!R】) of tumor mRNA to predict sensitivity of specimens to 5-fluorouracil.2005

    • Author(s)
      Kubota T, et al.
    • Total Pages
      257-265
    • Publisher
      Human Press Inc., New Jersey.
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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