2000 年度実績報告書

癌制御をめざしたMolecular Based Surgery体系の確立

研究課題

研究課題/領域番号	10307028
研究機関	大阪大学
研究代表者	門田守人大阪大学, 医学系研究科, 教授 (00127309)
研究分担者	有吉秀男大阪大学, 医学系研究科, 助手 (60294055) 中森正二大阪大学, 医学系研究科, 講師 (70294080) 塩崎均大阪大学, 医学系研究科, 助教授 (70144475) 大植雅之大阪大学, 医学系研究科, 助手 (40294095) 永野浩昭大阪大学, 医学系研究科, 助手 (10294050)
キーワード	進展度診断 / 遺伝子診断 / 微小転移 / 外科手術 / 再発
研究概要	癌の進展度診断において最も重要であるリンパ節転移の遺伝子レベルでの診断の可能性を検討した。その結果、癌遺伝子K-ras遺伝子変異が高率に認められる膵癌において、遺伝子変異の検出を指標とした微小リンパ節転移検出の可能性の検討を行い、実際の臨床例において、病理組織学的に転移が認められないリンパ節においてもこれらの遺伝子変異が検出され、微小転移存在の可能性が示唆された。さらに、遺伝子診断によるリンパ節転移診断によって、より正確に膵癌手術患者の予後予測が可能で江あることを見出した。また、K-rasやp53遺伝子変異の検出率が低い食道癌、胃癌、乳癌、肝癌、胆管癌等では、遺伝子診断の指標としてK-rasやp53遺伝子が利用しがたいため、上皮細胞分子マーカーであるサイトケラチン遺伝子、臓器特異的なAFP(α-fetoprotein)、腫瘍特異的抗原とされるMAGE遺伝子、マンモグロブリン遺伝子の発現性を指標としたリンパ節中や骨髄中、腹腔洗浄液中の微量癌細胞の検出の可能性を見い出した。しかし、これらの遺伝子診断をは定性的診断となるため、より正確な診断のため、定量的な遺伝子増幅法を用い、これら微小転移診断が定量的に行い得るか否かを検討し、一定のカットオフ値を設定することにより、診断結果が偽陽性となる可能性も低く、臨床応用が可能であることを見いだした。この他、癌の悪性化に関わる分子を検索し、プロスタグランジン合成に関わるCOX-2の発現が、膵癌、肝癌等で重要な働きをしていることを見いだし、COX-2阻害剤によるこれら癌の治療応用への可能性を見いだした。また、進行肝臓癌におけるインターフェロン併用化学療法の有効性を明らかにし、その効果発現の分子機構の解明を行った。

研究成果
(41件)

すべてその他

すべて文献書誌 (41件)

[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Sakon M.,Monden M. et al.: "Measurement of hepatocyte growth factor in serum and plasma"Int J Clin Lab Res. 29. 110-113 (1999)
[文献書誌] Tsujie M.,Monden M. et al.: "Expression of tumor suppressor gene p16INK4 products in primary gastric cancer"Oncology. 58. 126-136 (2000)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Takiguchi S.,Monden M., et al.: "Influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth"Surg Endos. 14. 41-44 (2000)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Yamada T.,Monden M. et al.: "Outcome of pancreatic cancer patients based on genetic lymph node staging "Int J Oncol. 16. 1165-1171 (2000)
[文献書誌] Shamma A.,Monden M. et al.: "Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus"Clin Can Res. 6. 1229-1238 (2000)
[文献書誌] Sakon M.,Monden M. et al.: "Hepatic resection of hepatocellular carcinomas based on tumor hemodynamics"J Surg Oncol. 73. 179-181 (2000)
[文献書誌] 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)
[文献書誌] Kondo M.,Monden M. et al.: "Expression of interferon α/β receptor in human hepatocellular carcinoma"Int J Oncol. 17. 83-88 (2000)
[文献書誌] 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)
[文献書誌] Okami J.,Monden M. et al.: "Genetic detection for micrometastasis in lymph node of biliary tract carcinoma"Clin Can Res. 6. 2326-2332 (2000)
[文献書誌] Yashiro K.,Monden M., et al.: "Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes"Genes to Cells. 5. 343-357 (2000)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)

2000 年度 実績報告書

癌制御をめざしたMolecular Based Surgery体系の確立

研究代表者

門田 守人 大阪大学, 医学系研究科, 教授 (00127309)

研究成果

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Sakon M.,Monden M. et al.: "Measurement of hepatocyte growth factor in serum and plasma"Int J Clin Lab Res. 29. 110-113 (1999)

[文献書誌] Tsujie M.,Monden M. et al.: "Expression of tumor suppressor gene p16INK4 products in primary gastric cancer"Oncology. 58. 126-136 (2000)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Takiguchi S.,Monden M., et al.: "Influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth"Surg Endos. 14. 41-44 (2000)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Yamada T.,Monden M. et al.: "Outcome of pancreatic cancer patients based on genetic lymph node staging "Int J Oncol. 16. 1165-1171 (2000)

[文献書誌] Shamma A.,Monden M. et al.: "Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus"Clin Can Res. 6. 1229-1238 (2000)

[文献書誌] Sakon M.,Monden M. et al.: "Hepatic resection of hepatocellular carcinomas based on tumor hemodynamics"J Surg Oncol. 73. 179-181 (2000)

[文献書誌] 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)

[文献書誌] Kondo M.,Monden M. et al.: "Expression of interferon α/β receptor in human hepatocellular carcinoma"Int J Oncol. 17. 83-88 (2000)

[文献書誌] 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)

[文献書誌] Okami J.,Monden M. et al.: "Genetic detection for micrometastasis in lymph node of biliary tract carcinoma"Clin Can Res. 6. 2326-2332 (2000)

[文献書誌] Yashiro K.,Monden M., et al.: "Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes"Genes to Cells. 5. 343-357 (2000)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

2000 年度実績報告書

門田守人大阪大学, 医学系研究科, 教授 (00127309)