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Optimization of cancer chemotherapy using DNA microarray

Research Project

Project/Area Number 13470111
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTohoku University

Principal Investigator

KANAMARU Ryunosuke  Tohoku University, Institute of development, aging and cancer, Professor, 加齢医学研究所, 教授 (70152783)

Co-Investigator(Kenkyū-buntansha) KATO Satoshi  Tohoku University, Institute of development, aging and cancer, Research associate, 加齢医学研究所, 助手 (60333887)
鈴木 貴夫  東北大学, 医学部・附属病院, 助手 (90292276)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥11,900,000 (Direct Cost: ¥11,900,000)
KeywordsMICROARRAY / CHEMOTHERAPY / OPTIMIZATION / DNAマイクロアレイ / 癌化学療法 / オーダーメイド治療
Research Abstract

DNA microarray based optimization of cancer chemotherapy is one of the urgent themes to solve. Practically chemotherapy are underwent by combination rather than single agent, so we think most important step to optimize the cancer chemotherapy is analyze the genes that related synergy of combined administration. We made custom 11K-cDNA microarray and examined gene expression changes with it. Colon cancer models are used. Colon cell line DLD1,LSI74T and 0VK18, MCF 7 cells for control are cultured in appropriate medium. In the first step ideal condition for synergy was determined. 5FU, cisplatin (CDDP) and camptothecin (CPT-11) are administered and cell growth are counted by MTT assay. Finally CDDP 0.5μg/ml, 5FU 5μM (CDDP+5FU) and CPT-11 10μM, 5FU 5μM(CPT-11+5FU) are found to be ideal for synergy. Many single agent related genes (for example inosine monophosphate dehydrogenase 1 and adenine phosphoinosyltransferase for 5FU and heat shock protein 90 and Y-box binding protein 1 (YB-1) for CDDP, keratin 8,18, tubulin beta for CPT-11) are picked up. CPT-11+ 5FU specific genes are NF-kB activating kinase and methionyl aminopeptidase and so on. CDDP + 5FU related genes are single strand DNA binding protein, presenillin associated protein…etc. Interestingly YB-1 was up-regulated in CDDP only. CDDP, 5FU concomitant administration did not show significant expression increase on YB-1. As YB-1 regulates MDR1, it may be newly found mechanism on CDDP-5FU synergy. Furthermore IER3 which play an important role on apoptosis in anti-apoptotic manner was found to be up-regulated on 5FU but not CPT-11+5FU, CDDP+5FU combination. There should be several previously unknown mechanisms on synergistic effect in combination chemotherapy. Our result strongly suggest important profile on gene expression changes and beneficial for searching such genes to understand and customize the effect on combination chemotherapy.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Murakawa Y., Kanamaru R.et al.: "α-FP normalization as a prognostic factor for mediastinal origin embryonal carcinoma"Internal Medicine. 41. 883-888 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Otsuka K., Kato S., Kanamaru R.et al.: "Analysis of the human APC mutation spectrum in a Saccharomyces cerevisiae strain with a mismatch repair defect"Int J. Cancer. 103. 624-630 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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