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Establishment of Molecular Based Surgery for Cancer Control

Research Project

Project/Area Number 10307028
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionOsaka University

Principal Investigator

MONDEN Morito  Osaka University Medical School of Medicine, Professor, 医学系研究科, 教授 (00127309)

Co-Investigator(Kenkyū-buntansha) ARIYOSHI Hideo  Osaka University Medical School of Medicine, Assistant Professor, 医学系研究科, 助手 (60294055)
NAKAMORI Shoji  Osaka University Medical School of Medicine, Lecturer, 医学系研究科, 講師 (70294080)
SHIOZAKI Hitoshi  Osaka University Medical School of Medicine, Assistant Professor, 医学系研究科, 助教授 (70144475)
OHUE Masayuki  Osaka University Medical School of Medicine, Assistant Professor, 医学系研究科, 助手 (40294095)
NAGANO Hiroaki  Osaka University Medical School of Medicine, Assistant Professor, 医学系研究科, 助手 (10294050)
冨田 尚裕  大阪大学, 医学部, 助手 (00252643)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥38,300,000 (Direct Cost: ¥38,300,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1998: ¥19,100,000 (Direct Cost: ¥19,100,000)
KeywordsGenetic diagnosis / Micrometastasis / Surgery / Endoscopic Surgery / Transplantation / Prognosis / Progression / 再発 / 癌進展 / Molecular Based Surgery / 外科治療
Research Abstract

Current strategy of treatment for solid cancer is based on curative resection of tumor due to histological examination of cancer spread such as tumor cell invasion, lymph node metastasis, and distant metastasis. Such examination, however, is not always accurate and fails to evaluate actual cancer cell spread. To establish molecular-based-surgery, we attempted to establish molecular detection of cancer cells in lymph node or circulation. We first established molecular gene marker for genetic detection for metastasis. We utilized K-ras gene mutation as a genetic marker for lymph node metastasis in pancreatic cancer and detection of K-ras gene mutations in lymph nodes may be clinically useful to assess the accurate tumor staging and to stratify the patient with pancreatic adenocarcinoma who are at high or low risk for recurrence after curative surgery. We also found that cytokeratin gene, α-fetoprotein gene, MAGE gene and manmoglobin B gene were suitable for genetic diagnostic marker in cancers which have a low frequency of K-ras mutation in tumors. Next, to overcome the weak point of qualitative genetic diagnosis, we established quantitative method for genetic diagnosis. Furthermore, we found that cyclooxygenase(COX)-2 plays an important role in carcinogenesis and progression in esophageal, liver and pancreatic cancers and that application of COX-2 inhibitor is potentially useful for cancer treatment. We also established a novel treatment for advanced liver cancer with chemotherapy combined with interferon a and revealed the molecular mechanism of the treatment. In clinical, we investigated the application of the minimal invasive surgery associated with endoscopy for cancer and feasibility of transplant surgery for cancer treatment.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (71 results)

All Other

All Publications (71 results)

  • [Publications] Aihara T, Monden M, et al.: "Mammaglobin B as a novel marker for detection of breast cancer micrometastases in axillary lymph nodes by reverse transcription-polymerase chain reaction"Breast Cancer Res Treat. 58. 137-140 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kondo M, Monden M, et al.: "Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma"Clin Can Res. 5(12). 4005-4012 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyake Y, Monden M, et al.: "Quantification of micrometastases in lymph nodes of colorectal cancer using real-time fluorescence polymerase chain reaction"Int J Oncol. 16. 289-293 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamada T, Monden M, et al.: "Outcome of pancreatic cancer patients based on genetic lymph node staging"Int J Oncol. 16. 1165-1171 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shamma A, Monden M, et al.: "Up-regulation of cyclooxygenase-2 in squamous carcino genesis of the esophagus"Clin Can Res. 6. 1229-1238 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okami J, Monden M, et al.: "Genetic detection for micrometastasis in lymph node of biliary tract carcinoma"Clin Can Res. 6. 2326-2332 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eguchi H, Monden M, et al.: "Augmentation of antitumor activity of 5-fluorouracil by interferon α is associated with up-regulation of p27Kipl in human hepatocellular carcinoma cells"Clin Can Res. 6(7). 2881-2890 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kondo M, Monden M, et al.: "Expression of interferon α/βreceptor in human hepatocellular carcinoma."Int J Oncol. 17. 83-88 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto A, Monden M, et al.: "Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma."Dig Dis Sci. 45(7). 1376-1382 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto A, Monden M, et al.: "Clinical application of quantative analysis for detection of hematogenous spread of hepatocellular carcinoma by real-time PCR."Int J Oncol. 18. 527-532 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aihara T, Monden M, et al.: "Mammaglobin B as a novel marker for detection of breast cancer micrometastases in axillary lymph nodes by reverse transcription-polymerase chain reaction"Breast Cancer Res Treat. 58. 137-140 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kondo M, Monden M, et al.: "Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma"Clin Can Res. 5(12). 4005-4012 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyake Y, Monden M, et al.: "Quantification of micrometastases in lymph nodes of colorectal cancer using real-time fluorescence polymerase chain reaction"Int J Oncol. 16. 289-293 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamada T, Monden M, et al.: "Outcome of pancreatic cancer patients based on genetic lymph node staging"Int J Oncol. 16. 1165-1171 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shamma A, Monden M, et al.: "Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus"Clin Can Res. 6. 1229-1238 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okami J, Monden M, et al.: "Genetic detection for micrometastasis in lymph node of biliary tract carcinoma"Clin Can Res. 6. 2326-2332 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eguchi H., Monden M, et al.: "Augmentation of antitumor activity of 5-fluorouracil by interferon α is associated with up-regulation of p27Kipl in human hepatocellular carcinoma cells"Clin Can Res. 6(7). 2881-2890 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kondo M, Monden M, et al.: "Expression of interferon α/β receptor in human hepatocellular carcinoma."Int J Oncol. 17. 83-88 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto A, Monden M, et al.: "Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma."Dig Dis Sci. 45(7). 1376-1382 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto A, Monden M, et al.: "Clinical application of quantative analysis for detection of hematogenous spread of hepatocellular carcinoma by real-time PCR."Int J Oncol. 18. 527-532 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aihara T.,Monden M. et al.: "Mammaglobin B as a novel marker for detection of breast cancer micrometastases in axillary lymph nodes by reverse transcription-polymerase chain reaction"Breast Cancer Res Treat. 58. 137-140 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ito Y.,Monden M. et al.: "Both cell proliferation and apoptosis signiflcantly predict shortened disease-free survival in hepatocellular carcinoma"Br J Cancer. 81(4). 747-751 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kondo M.,Monden M. et al.: "Increased expression of COX-2 in nontumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma"Clin Can Res. 5(12). 4005-4012 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa H.,Monden M., et al.: "APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor, binds to p53-binding protein 2 and translocates it to the perinucleus"Cancer Res. 60. 101-105 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yano M.,Monden M. et al.: "Preoperative intranasal mupirocin ointment significantly reduces postoperative infection with Staphylococcus aureus in patients undergoing upper gastrointestinal surgery"Surg Today. 30. 16-21 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa H.,Monden M., et al.: "EB3, a novel member of the EB1 family preferentially expressed in the central nervous system, binds to a CNS-specific APC homologue"Oncogene. 19. 210-216 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakon M.,Monden M. et al.: "Measurement of hepatocyte growth factor in serum and plasma"Int J Clin Lab Res. 29. 110-113 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsujie M.,Monden M. et al.: "Expression of tumor suppressor gene p16INK4 products in primary gastric cancer"Oncology. 58. 126-136 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shamma A.,Monden M. et al.: "Loss of p27KIP1 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma"Oncology. 58. 152-158 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Bilchik A.,Monden M., et al.: "Molecular detection of metastatic pancreatic carcinoma cells using a multimarker reverse transcriptase-polymerase chain reaction assay"Cancer. 88(5). 1037-1044 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takiguchi S.,Monden M., et al.: "Influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth"Surg Endos. 14. 41-44 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kadota M.,Monden M. et al.: "Identification of a 7-cM region of frequent allelic loss on chromosome band 16p13.3 that is specifically associated with anaplastic thyroid carcinoma"Oncol Rep. 7. 529-533 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ooka M.,Monden M. et al.: "Selection of mRNA markers for detection of lymph node micrometastases in breast canacer patients"Oncol Rep. 7. 561-566 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujimura H.,Monden M., et al.: "Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia"Thrombos Res. 98. 1-8 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiwara Y.,Monden M. et al.: "PTEN/MMAC1 mutation and frequent loss of heterozygosity identified in chromosome 10q in a subset of hepatocellular carcinomas"Jpn J Cancer Res. 91. 287-292 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aihara T.,Monden M. et al.: "Mammaglobin B gene as a novel marker for lymph node micrometastasis in patients with abdominal cancers"Cancer Letters. 150. 79-84 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shamma A.,Monden M. et al.: "Cyclin D1 overexpression in esophageal dysplasia : a possible biomarker for carcinogenesis of esophageal squamous cell carcinoma"Int J Oncol. 16. 261-266 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyake Y.,Monden M. et al.: "Quantification of micrometastases in lymph nodes of colorectal cancer using real-time fluorescence polymerase chain reaction"Int J Oncol. 16. 289-293 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiwara Y.,Monden M. et al.: "Assessment of stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers"Int J Oncol. 16. 799-804 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shiozaki H.,Monden M. et al.: "Clinical application of malignancy potential grading as a prognostic factor of human esophageal cancers"Surgery . 127(5). 552-561 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiwara Y.,Monden M. et al.: "Prevention of cross-contamination during sampling procedure in molecular detection for cancer micrometastasis"Cancer Letters. 153. 109-111 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaneko K.,Monden M. et al.: "Establishment of a visible peritoneal micrometastatic model from a gastric adenocarcinoma cell line by green fluorescent protein"Int J Oncol. 16. 893-898 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamada T.,Monden M. et al.: "Outcome of pancreatic cancer patients based on genetic lymph node staging "Int J Oncol. 16. 1165-1171 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shamma A.,Monden M. et al.: "Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus"Clin Can Res. 6. 1229-1238 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakon M.,Monden M. et al.: "Hepatic resection of hepatocellular carcinomas based on tumor hemodynamics"J Surg Oncol. 73. 179-181 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Grochowiecki T.,Monden M. et al.: "Induction of unresponsiveness to islet xenograft by MMC treatment of graft and blockage of LFA-1/ICAM-1 pathway"Transplantation. 69(8). 1567-1571 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kondo M.,Monden M. et al.: "Expression of interferon α/β receptor in human hepatocellular carcinoma"Int J Oncol. 17. 83-88 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Amano M.,Monden M. et al.: "Selective augmentations of intratumoral 5-fluorouracil concentration by local immunotherapy with OK-432 and fibrinogen"Dic Colon Rectum. 43(3). 402-407 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okami J.,Monden M. et al.: "Genetic detection for micrometastasis in lymph node of biliary tract carcinoma"Clin Can Res. 6. 2326-2332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yashiro K.,Monden M., et al.: "Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes"Genes to Cells. 5. 343-357 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takemasa I.,Monden M. et al.: "Overexpression of CDC25B phosphatase as a novel marker of poor prognosis of human colorectal carcinoma"Cancer Res. 60. 3043-3050 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamano T.,Monden M., et al.: "Amplification of transgene expression in Vitro and in Vivo using a novel inhibitor of histone deacetylase"Molecular Therapy. 1(6). 574-580 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kishimoto S.,Monden M., et al.: "The inhibitory effect of prostaglandin E1 on oxidative stress-induced hepatocyte injury evaluated by calpain-μ activation"Transplantation. 69(11). 2314-2319 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okamura S.,Monden M., et al.: "Identiflcation of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system"Oncol Res. 11. 281-285 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Eguchi H.,Monden M. et al.: "Augmentation of antitumor activity of 5-fluorouracil by interferon α is associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells"Clin Can Res. 6(7). 2881-2890 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aono Y.,Monden M. et al.: "Human umbilical vein endothelial cells (HUVECs) show Ca2+ mobilization as well as Ca2+ influx upon hypoxia"J Cell Biochem. 78. 458-464 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawanishi K.,Monden M. et al.: "Correlation between loss of E-cadherin expression and overexpression of autocrine motility factor receptor in association with progression of human gastric cancers"Am J Clin Pathol. 113(2). 266-274 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imai Y.,Monden M., et al.: "Superparamagnetic iron oxide-enhanced magnetic resonance images of hepatocellular carcinoma : correlation with histological grading"Hepatology. 32(2). 205-212 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Eguchi H.,Monden M. et al.: "Presence of active hepatitis associated with liver cirrhosis is a risk factor for mortality caused by posthepatectomy liver failure"Dig Dis Sci. 45(7). 1383-1388 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masude N.,Monden M. et al.: "Clinical significance of micrometastases in axillary lymph nodes assessed by reverse transcription-polymerase chain reaction in breast cancer patients"Clin Can Res. 6(11). 4176-4185 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yano M.,Monden M. et al.: "Squamous cell carcinoma of the esophagus infiltrating the respiratory tract is less sensitive to preoperative concurrent radiation and chemotherapy"J Am Coll Surg . 191(6). 626-634 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okami J, Monden M, et al.: "Overexpression of cyclooxgenase-2 in carcinoma of the pancreas"Clin Cancer Res. 5. 2018-2024 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito Y, Monden M, et al.: "Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma : p27 independently predicts the recurrence"Hepatology. 30. 90-99 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kondo M, Monden M, et al.: "Increased expression of COX-2 in non-tumor liver tissue is associated with shorter disease-free survival in patients with hepatocellular carcinoma"Clin Cancer Res. 5. 4005-4012 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Gofuku J, Shiozaki H, et al.: "Expression of E-cadherin and α -catenin in patients with colorectal carcinoma. Correlation with cancer invasion and metastasis"Am J Clin Pathol. 111. 29-37 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshioka K, Nakamori S, et al.: "Overexpression of small GTP-binding protein Rho promotes invasion of tumor cells"Cancer Res. 59. 2004-2010 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyake Y, Ohue M, et al.: "Quantification of micrometastases in lymph nodes of colorectal cancer using real-time fluorescence polymerase chain reaction"Int J Oncol. 16. 289-293 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada T.: "Detection of K-ras Gene Mutations in Plasma DNA of Patients with Pancreatic Adenocarcinoma : Correlation with Clinicopathological Features 1." Clin.Cancer Re.4. 1527-1532 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aihara T.: "Allelic Imbalance of insulin-like Growth Factor II Gene Expression in Cancerous and Precancerous Lesions of the liver" Hepatology. 28(1). 86-89 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Imamura H.: "Rho and Rob small G proteins coordinately reorganize stress fibers and focal adhesions in MDCK cells" Mol.Biol.Cell.9. 2561-2575 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohnishi T.: "Identification of a Novel Gene Marker Specific for Epithelial Cells by Utilizing a 3'-directed cDNA Library" Cancer Res.58. 2440-2444 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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