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Prediction of sensitivity of rectal cancer in response to preoperative radiotherapy and chemoradiotherapy by DNA microarray analysis-Anew strategy for individualized tailored therapy ofrectal cancer

Research Project

Project/Area Number 18390361
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTeikyo University

Principal Investigator

WATANABE Toshiaki  Teikyo University, School of Medicine, Professor (80210920)

Co-Investigator(Kenkyū-buntansha) MATSUDA Keiji  Teikyo University, School of Medicine, Lecturer (90302728)
NOZAWA Kejiro  Teikyo University, School ofMedicine, Assistant Professor (90317686)
IINUMA Hisae  Teikyo University, School of Medicine, Lecturer (30147102)
味村 俊樹  帝京大学, 医学部, 講師 (20262131)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥15,450,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2007: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2006: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsRectal Cancer / DNA Microarrav / Prediction of response / Radiotherapy / Chemo radiotheranv / 方射線療法
Research Abstract

Local recurrence is one of the major forms of recurrence after surgery for rectal cancer. Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, in the clinical settings, the response to radiotherapy differs among individual tumors. Therefore, to select patients who respond to radiotherapy is very important to perform radiotherapy effectively. We aimed to identify a set of discriminating genes that can be used for characterization and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal cancer patients who underwent preoperative radiotherapy were studied. Biopsy specimens were obtained from rectal cancer before preoperative radiotherapy. Response to radiotherapy was determined by histopathologic examination of surgically resected specimens and classified as responders or nonresponders. By determining gene expression profiles using human U95Av2 Gene Chip, we identified 33 … More novel discriminating genes of which the expression differed significantly between responders and nonresponders. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with an accuracy of 82.4%. Using the same strategy, we further performed a study to build a predictive model for chemoradiotherapy for rectal cancer. We examined a total of 15 patients who underwent preoperative chemoradiotherapy for rectal cancer. The patients underwent surgery after chemoradiotherapy using oral 5-FU(Fluorouracil) drugs. Response to chemoradiotherapy was determined by histological examination of surgically resected specimens as described above. By gene expression analysis, we could build a model which could predict the response to chemoradiotherapy with an accuracy of 100%. Although the number of examined patients is not large, these results suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy and chemoradiotherapy to establish an individualized tailored therapy for rectal cancer. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (54 results)

All 2008 2007 2006

All Journal Article (54 results) (of which Peer Reviewed: 18 results)

  • [Journal Article] Loss of Smad4 protein expression and 18qLOH as molecular markers indicating lymph node metastasis in colorectal cancer-a study matched for tumor depth and pathology2008

    • Author(s)
      Tanaka T, Watanabe T, Kazama Y, et. al.
    • Journal Title

      Journal of Surgical Oncology 97(1)

      Pages: 69-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Loss of Smad4 protein expression and 18qLOH as .molecular markers indicating lymph node metastasis in colorectal cancer-a study matched for tumor depth and pathology2008

    • Author(s)
      Tanaka, T., Watanabe, T., Kazama, Y., et. al.
    • Journal Title

      Journal of Surgical Oncology 97(1)

      Pages: 69-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Loss of Smad4 protein expression and 18qLOH as molecular markers in dicating lymph node metastasis in colorectal cancer-a study matched for tumor depth and pathology.2008

    • Author(s)
      Tanaka T, Watanabe T, Kazama Y, et. al.
    • Journal Title

      J Surg Oncol 97(1)

      Pages: 69-73

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of 5-fluorouracil metabollic enzyme genes in Dukes' stage B and C colorectal cancer patients treated with oral 5-fluorouracil-based adjuvant chemotherapy.2008

    • Author(s)
      Yamada H, Iinuma H, Watanabe T.
    • Journal Title

      Oncol Rep 19(3)

      Pages: 729-35

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray2007

    • Author(s)
      Watanabe T, Kobunai T, Toda E, et. al.
    • Journal Title

      Clinical Cancer Research 13(2)

      Pages: 415-420

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum:relationship to clinicopathological features2007

    • Author(s)
      Kazama Y, Watanabe T, Kanazawa T, et. al.
    • Journal Title

      Journal of Clinical Pathology 60(6)

      Pages: 701-4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The 4-portal technique decreases adverse effects in preoperative radiotherapy for advanced rectal cancer:comparison between the 2-portal and the 4-portal techniques2007

    • Author(s)
      Kiyomatsu T, Watanabe T, Muto T, et. al.
    • Journal Title

      American Journal of Surgery 194(4)

      Pages: 542-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gene expression signature and the prediction of ulcerative colitis associated colorectal cancer by DNA microarray2007

    • Author(s)
      Watanabe, T., Kobunai, T., Toda, E., et. al.
    • Journal Title

      Clinical Cancer Research 13(2)

      Pages: 415-420

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum : relationship to clinicopathological features2007

    • Author(s)
      Kazama, Y., Watanabe, T., Kanazawa, T., et. al.
    • Journal Title

      Journal of Clinical Pathology 60(6)

      Pages: 701-4

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The 4-portal technique decreases adverse effects in preoperative radiotherapy for advanced rectal cancer : comparison between the 2-portal, and the 4-portal techniques2007

    • Author(s)
      Kiyomatsu, T., Watanabe, T., Muto, T., et. al.
    • Journal Title

      American Journal of Surgery 194(4)

      Pages: 542-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gene expression signature and the prediction of ulcerative colitis asso ciated colorectal cancer by DNA microarray.2007

    • Author(s)
      Watanabe T, Kobunai T, Toda E, et. al.
    • Journal Title

      Clin Cancer Res 13(2)

      Pages: 415-420

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid genetic diagnosis with transcription-reverse transcription concerted reaction system for peritoneal recurrence and survival in colorectal cancer patients.2007

    • Author(s)
      Hayama T, Iinuma H, Watanabe T.
    • Journal Title

      Oncol Rep 18(4)

      Pages: 779-784

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial growth factor-C(VEGF-C) is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer.2007

    • Author(s)
      Kazama S, Watanabe T, Kanazawa T, et. al.
    • Journal Title

      Hepatogastroenterology 54(73)

      Pages: 71-76

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of ribosomal p70 S6 kinase and rapamycin sensitivity in human colorectal cancer.2007

    • Author(s)
      Nozama H, Watanabe T, Nagawa H.
    • Journal Title

      Cancer Lett 251(1)

      Pages: 105-13

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Left-Sided microsatellite unstable colorectal cancers show less frequent methylation of hMLH1 and CpG island methylator phenotype than right-seded ones.2007

    • Author(s)
      Tanaka J, Watanabe T, Kanazawa T, et. al.
    • Journal Title

      J Surg Oncol 96(7)

      Pages: 611-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum:relationship to clinicopathological features.2007

    • Author(s)
      Kazama Y, Watanabe T, Kanazawa T, et. al.
    • Journal Title

      J Clin Pathol 60(6)

      Pages: 701-4

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The4-portal technique decreases adversee effects in preoperative radiotherapy for advanced rectal cancer;comparison between the 2-portal and the4-portal techniques.2007

    • Author(s)
      Kiyomatsu T, Watanabe T, MutoT, et. al.
    • Journal Title

      Am J Surg 194(4)

      Pages: 542-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perioperative radiation for rectal cancer and sexual dysfunction after T ME: cause and effect?2007

    • Author(s)
      Konishi T, Watanabe T, Kiyomatsu T, et. al.
    • Journal Title

      Ann Surg 245(1)

      Pages: 155-155

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression signature and the prediction of ulcerative colitis associated colorectal cancer by DNA microarray.2007

    • Author(s)
      Watanabe T, Kobunai T, Tobe E, et al.
    • Journal Title

      Clinical Cancer Research 13(2)

      Pages: 415-20

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Adjuvant chemotherapy in colorectal cancer patients with microsatellite instability.2007

    • Author(s)
      Watanabe T, Kanazawa T, Kazama Y, et al.
    • Journal Title

      Clinical Cancer Research 12(12)

      Pages: 3866-7

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distal colorectal cancers with microsatellite instability(MSI)display distinct gene expression profiles that are different from proximal MSI cancers2006

    • Author(s)
      Watanabe T, Kobunai T, Toda E, et. al.
    • Journal Title

      Cancer Research 66(20)

      Pages: 9804-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis:a study matched for T-and N-classification2006

    • Author(s)
      Tanaka T, Watanabe T, Kazama Y, et. al.
    • Journal Title

      British Journal of Cancer 95(11)

      Pages: 1562-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Risk factors for anastomotic leakage after surgery for colorectal cancer:results of prospective surveillance2006

    • Author(s)
      Konishi T, Watanabe T, Kishimoto J, et. al.
    • Journal Title

      Journal of The American College of Surgeons 202(3)

      Pages: 439-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prospective surveillance effectively reduced surgical site infections in elective colorectal surgery at a university hospital in Japan2006

    • Author(s)
      Konishi T, Watanabe T, Morikane K, et. al.
    • Journal Title

      Infection Control And Hospital Epidemiology 27(5)

      Pages: 1051-2

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Distal colorectal cancers with microsatellite instability(MSI) display distinct gene expression profiles that are different from proximal MSI cancers2006

    • Author(s)
      Watanabe, T., Kobunai, T., Toda, E., et. al.
    • Journal Title

      Cancer Research 66(20)

      Pages: 9804-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis : a study matched for T- and N- classification2006

    • Author(s)
      Tanaka, T., Watanabe, T., Kazama, Y., et. al.
    • Journal Title

      British Journal of Cancer 95(11)

      Pages: 1562-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Risk factors for anastomotic leakage after surgery for colorectal cancer : results of prospective surveillance2006

    • Author(s)
      Konishi, T., Watanabe, T., Kishimoto, J., et. al.
    • Journal Title

      Journal of The American College of Surgeons 202(3)

      Pages: 439-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prospective surveillance effectively reduced surgical site infections in elective colorectal surgery at a university hospital in Japan2006

    • Author(s)
      onishi, T., Watanabe, T., Morikane, K., et. al.
    • Journal Title

      Infection Control And Hospital Epidemiology 27(5)

      Pages: 1051-2

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles.2006

    • Author(s)
      Watanabe T, Komuro Y, Kiyomatsu T, et al.
    • Journal Title

      Cancer Research 66(7)

      Pages: 3370-4

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distal colorectal cancers with microsatellite instability (MSI) display distinct gene expression profiles that are different from proximal MSI cancers.2006

    • Author(s)
      Watanabe T, Kobunai T, Tobe E, et al.
    • Journal Title

      Cancer Research 66(20)

      Pages: 9804-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Weekly oxaliplatin and preoperative radiotherapy as a new neoadjuvant therapy for locally-advanced rectal cancer.2006

    • Author(s)
      Watanabe T, Kiyomatsu T, Kanazawa T, et al.
    • Journal Title

      Annals of Oncology 17(7)

      Pages: 1173-1173

    • Related Report
      2006 Annual Research Report
  • [Journal Article] SMAD4 levels and allelic imbalance in 18q21 in colorectal cancer.2006

    • Author(s)
      Watanabe T, Kanazawa T, Kazama Y, et al.
    • Journal Title

      Clinical Cancer Research 12(5)

      Pages: 1654-5

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Microsatellite Instability in adenoma as a possible marker to identify HNPCC patients.2006

    • Author(s)
      Watanabe T, Kanazawa T, Kazama Y, et al.
    • Journal Title

      American Jounal of Gastroenterology 101(1)

      Pages: 204-204

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Predictive value ob microsatellite instability for benefit from adjuvant fluorouracil chemotherapy in colorectal cancer.2006

    • Author(s)
      Iacopetta B, Watanabe T.
    • Journal Title

      Gut 55(11)

      Pages: 1671-2

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis : a study matched for T-and N-classification.2006

    • Author(s)
      Tanaka T, Watanabe T, Kazama Y, et al.
    • Journal Title

      British Journal of Cancer 95(11)

      Pages: 1562-7

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mucinous colorectal cancers with chromosomal instability : a biologically distinct and aggressive subtype.2006

    • Author(s)
      Kazama Y, Watanabe T, Kanazawa T, et al.
    • Journal Title

      Diagnostic Molecular Pathology 15(1)

      Pages: 30-4

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tumor budding at the deepest invasive margin correlates with lymph node metastasis in submucosal colorectal cancer detected by anticytokeratin antibody CAM5.2.2006

    • Author(s)
      Kazama S, Watanabe T, Ajioka Y, et al.
    • Journal Title

      British Journal of Cancer 94(2)

      Pages: 293-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Overexpression of hRFI inhibits 5-fluorouracil-induced apoptosis in colorectal cancer cells via activation of NF-kappaB and upregulation of BCL-2 and BCL-XL.2006

    • Author(s)
      Konishi T, Sasaki S, Watanabe T, et al.
    • Journal Title

      Oncogene 25(22)

      Pages: 3160-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elective Colon and Rectal Surgery Differ in Risk Factors for Wound Infection : Results ob Prospective Surveillance.2006

    • Author(s)
      Konishi T, Watanabe T, Kishimoto J, et al.
    • Journal Title

      Annals of Surgery 244(5)

      Pages: 758-63

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis induces acute deterioration of mucosal blood flow.2006

    • Author(s)
      Konishi T, Watanabe T, Kishimoto J, et al.
    • Journal Title

      Diseases of the Colon and Rectum 49(4)

      Pages: 530-1

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Risk factors for anastomotic leakage after surgery for colorectal cancer : results of prospective surveillance.2006

    • Author(s)
      Konishi T, Watanabe T, Kishimoto J, et al.
    • Journal Title

      Journal of The American College of Surgeons 202(3)

      Pages: 439-44

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prospective surveillance effectively reduced surgical site infections in elective colorectal at a university hospital in Japan2006

    • Author(s)
      Konishi T, Watanabe T, Morikane K, et al.
    • Journal Title

      Infection Control And Hospital Epidemiology 27(5)

      Pages: 526-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Site distribution of gastrointestinal carcinoids differs between races.2006

    • Author(s)
      Konishi T, Watanabe T, Muto T, et al.
    • Journal Title

      Gut 55(7)

      Pages: 1051-2

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Difference in incidence of colorectal cancer between men and women in Asia2006

    • Author(s)
      Konishi T, Watanabe T, Muto T, et al.
    • Journal Title

      Lancet Oncology 7(2)

      Pages: 104-5

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pelvic drainage should be a routine for TME with or without radiation.2006

    • Author(s)
      Konishi T, Watanabe T, Nagawa H.
    • Journal Title

      Annals of Surgery 241(1)

      Pages: 141-2

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Treatment of local ischaemia : another promising approach for gastrointestinal complications of pelvic radiotherapy.2006

    • Author(s)
      Konishi T, Watanabe T, Nagawa H.
    • Journal Title

      Gut 55(8)

      Pages: 1209-1209

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Surveillance colonoscopy should be conducted in patients with colorectal Shistosomiasis even after successful treatment of the disease.2006

    • Author(s)
      Konishi T, Watanabe T, Shibahara J, et al.
    • Journal Title

      Intemational Journal of Immunopathology and Pharmacology 19(1)

      Pages: 245-6

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cytomegalovirus infection in ulcerative colitis.2006

    • Author(s)
      Kojima T, Watabe T, Hata K, et al.
    • Journal Title

      Scandinavian Journal of Gastroentelology 41(6)

      Pages: 706-11

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lysophosphatidic acid-induced effects in human colon carcinoma DLD1 cells are partially dependent on transactivation of epidermal growth factor receptor.2006

    • Author(s)
      Mori K, Kitayama J, Shiba D, et al.
    • Journal Title

      Journal of Surgical Research 132(1)

      Pages: 56-61

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Telomerase subunit immunoreactivity and recurrence in colorectal cancer.2006

    • Author(s)
      Ohnishi T, Watanabe T, Nozawa H, et al.
    • Journal Title

      Hepatogastroenterologyogy 53(68)

      Pages: 188-91

    • Related Report
      2006 Annual Research Report
  • [Journal Article] hRFI overexpressed in HCT116 cells modulates Bcl-2family proteins when treated with 5-Fluorouracil.2006

    • Author(s)
      Sasaki S, Watanabe T, Kobunai T, et al.
    • Journal Title

      Oncology Reports 15(5)

      Pages: 1293-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of cystathionine beta-synthase variant 844ins68bq and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5-FU efficacy and doubling time.2006

    • Author(s)
      Sasaki S, Watanabe T, Kobunai T, et al.
    • Journal Title

      Cancer Letters 241(2)

      Pages: 256-62

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chronic colitis promotes tumor development.2006

    • Author(s)
      Shinozaki S, Watanabe T, Sato H, et al.
    • Journal Title

      Oncology Reports 15(6)

      Pages: 1485-90

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Toxic megacolon associated with Crohn's disease.2006

    • Author(s)
      Tsuchiya T, Watanabe T, Konishi T, et al.
    • Journal Title

      Gastrointestinal Endoscopy 64(6)

      Pages: 1012-3

    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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