2002 年度実績報告書

消化器難治癌の分子病態解析と臨床像解析を軸に展開する先進的治療法の開発

研究課題

研究課題/領域番号	12307026
研究機関	京都大学
研究代表者	今村正之京都大学, 医学研究科, 教授 (00108995)
研究分担者	土井隆一郎京都大学, 医学研究科, 講師 (20301236) 嶋田裕京都大学, 医学研究科, 講師 (30216072) 小野寺久京都大学, 医学研究科, 助教授 (50240825) 有井滋樹東京医科歯科大学, 医歯学総合研究科, 教授 (50151171) 山崎誠二京都大学, 医学研究科, 助手 (50303839)
キーワード	マイクロアレイ解析 / EGF-STAT情報伝達 / 分化誘導療法 / ペプチド導入療法 / ドーマントセラピー / 血管新生阻害療法
研究概要	食道癌の研究でEGFの増殖抑制作用にはSTAT1が関与していることを報告してきたが、さらにSTAT1ドミナントネガティブ導入株は腹膜播種を来すことが判明し、マイクロアレイ解析からその作用にMMPの関与が示唆された。INFγ投与でヌードマウス移植食道癌細胞株の増殖が抑制され、STATを介した食道癌治療の臨床応用の可能性が示唆された。EGFおよびINFγの反応不良株の機序解明ではレセプターの発現低下、STAT1リン酸化異常等の関与が示唆された。食道癌のマイクロアレイとartificial neural network解析(ANN)によりリンパ節転移に関与する約60の遺伝子を同定し、それによりリンパ節転移が85%と高率に予測できることを明らかとした。膵臓癌研究の分野ではcadherin, integrinの癌細胞の浸潤・転移における関与機序を臨床膵癌組織、臨床病理学データ、膵癌細胞株において示した.またケモカインとケモカイン受容体が膵癌の浸潤移転に関与していることを示し,転移抑制物質としてケモカイン受容体であるCXCR4の拮抗剤TN14003を開発した.膵癌は放射線治療,化学療法剤に抵抗性であるが,その原因としてアポトーシス抵抗性であることをBaX/Bcl-XLの不均衡,Fas-Fas ligandシステムの破綻,survivinの関与,Smacの関与について示した.強力な血管新生因子VEGFの受容体であるFlt-1の可溶型(sFlt)をHVJリポソームに封入してHVJ-Fexを作成し、これをMKN45胃癌細胞株のマウス腹膜播種モデルに投与して、腫瘍増殖抑制効果および生存期間延長効果を報告した。大腸癌細胞創部再発モデルにおいて、sFltを遺伝子導入した自家線維芽細胞を腹腔内投与し、優れた創部再発抑制効果を認めた。

研究成果
(23件)

すべてその他

すべて文献書誌 (23件)

[文献書誌] Ding Y, et al.: "Clinicopatholigical significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma"Oncology. 63. 378-384 (2002)
[文献書誌] Komoto I, et al.: "The Expression and function of calcium-sensing receptor in pancreatic Islet and insulinoma Cells"Pancreas. (in press). (2002)
[文献書誌] Li Z, et al.: "Inhibitory dffects of epigallocatechin-3-gallate on N-nitrosomethylbenzylamin-induced esophageal tumorigenesis in F344 rats"Int J Oncol. 21. 1275-1283 (2002)
[文献書誌] Li Z, et al.: "Promotion effects of hot water on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in F344 rats"Oncol Reports. (in press). (2002)
[文献書誌] Shimada Y, et al.: "Indication of the abdominal para-aortic lymph-node dissection for patients with esophageal squamous cell carcinoma"Surgery. 132. 93-99 (2002)
[文献書誌] Li Z, et al.: "Suppression of N-nitrosomethylbenzylamine (NMBA)-induced Esophageal Tumorigenesis in F344 Rats by Resveratrol"Carcinogenesis. 23. 1531-1536 (2002)
[文献書誌] Kawabe A, et al.: "Expression of Cyclooxygenase-2 in primary and remnant gastric carcinoma : Comparing it with p53 accumulation. Helicobacter pylori infection, and vascular endotholial growth factor expression"J Surg Oncol. 80. 79-88 (2002)
[文献書誌] Mizumoto M, et al.: "A novel suicide gene therapy system for p53-mutated cells using a wild-type p53-specific promoter and Cre/loxP switch"Surg Today. 32. 53-58 (2002)
[文献書誌] Hosotani R, et al.: "Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice"Clin Cancer Res. 8(4). 1271-1276 (2002)
[文献書誌] Lee JU, et al.: "Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells"Eur J Cancer. 38(11). 1526-1534 (2002)
[文献書誌] Doi R, et al.: "Surgical management of intraductal papillary mucinous tumor of pancreas"Surgery. 132(1). 80-85 (2002)
[文献書誌] Wada M, et al.: "Intravenous calcium injection test is a novel complementary procedure in differential diagnosis for gastrinoma"World J Surg. 26(10). 1291-1296 (2002)
[文献書誌] Iwakura H, et al.: "Ghrelin expression in islet cell tumors : augmented expression of ghrelin in a case of glucagonoma with multiple endocrine neoplasm type I"J Clin Endocrinol Metab. 87(11). 4885-4888 (2002)
[文献書誌] Masui T, et al.: "Expression of IL-6 receptor in pancreatic cancer : involvement in VEGF induction"Anticancer Res. 22(6C). 4093-4100 (2002)
[文献書誌] Sato F, et al.: "Paratracheal lymph node metastasis is associated with cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma"Ann Surg Oncol. 9. 65-70 (2002)
[文献書誌] Nakamura Y, et al.: "High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria"Endocrine. 19(2). 127-130 (2002)
[文献書誌] Nagayama S, et al.: "Genome-wide analysis of gene expression in synovial sarcoma using a cDNA microarray"Cancer Research. 62. 5859-5866 (2002)
[文献書誌] Nagayama S, et al.: "Alterd exprsssion of the receptor and ligand in the TGFb signaling pathway in diffusely infiltrating colon carcinoma"Anti Cancer Research. 22. 3545-3554 (2002)
[文献書誌] Nakau M, et al.: "Hepatocellular carcinoma caused by loss of heterozygosity in Lkb1 gene knockout mice"Cancer Research. 62. 4549-4553 (2002)
[文献書誌] Ogawa M, et al.: "Direct electrophilic radiofluorination of a cyclic RGD peptide for in vivo αvβ3 integrin related tumor imaging"Nucl Med Biol. 30. 1-9 (2003)
[文献書誌] Tulachan S, et al.: "All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas"Diabetes. 52(1). 76-84 (2003)
[文献書誌] Shimada Y, et al.: "Cell culture in esophageal squamous cell carcinoma and the association with molecular markers"Clin Cancer Res. (in press). (2003)
[文献書誌] Imaura M: "Superficial Esophageal Neoplasm"Springer. Tokyo. 1-240 (2002)

2002 年度 実績報告書

消化器難治癌の分子病態解析と臨床像解析を軸に展開する先進的治療法の開発

研究代表者

今村 正之 京都大学, 医学研究科, 教授 (00108995)

研究成果

[文献書誌] Ding Y, et al.: "Clinicopatholigical significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma"Oncology. 63. 378-384 (2002)

[文献書誌] Komoto I, et al.: "The Expression and function of calcium-sensing receptor in pancreatic Islet and insulinoma Cells"Pancreas. (in press). (2002)

[文献書誌] Li Z, et al.: "Inhibitory dffects of epigallocatechin-3-gallate on N-nitrosomethylbenzylamin-induced esophageal tumorigenesis in F344 rats"Int J Oncol. 21. 1275-1283 (2002)

[文献書誌] Li Z, et al.: "Promotion effects of hot water on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in F344 rats"Oncol Reports. (in press). (2002)

[文献書誌] Shimada Y, et al.: "Indication of the abdominal para-aortic lymph-node dissection for patients with esophageal squamous cell carcinoma"Surgery. 132. 93-99 (2002)

[文献書誌] Li Z, et al.: "Suppression of N-nitrosomethylbenzylamine (NMBA)-induced Esophageal Tumorigenesis in F344 Rats by Resveratrol"Carcinogenesis. 23. 1531-1536 (2002)

[文献書誌] Kawabe A, et al.: "Expression of Cyclooxygenase-2 in primary and remnant gastric carcinoma : Comparing it with p53 accumulation. Helicobacter pylori infection, and vascular endotholial growth factor expression"J Surg Oncol. 80. 79-88 (2002)

[文献書誌] Mizumoto M, et al.: "A novel suicide gene therapy system for p53-mutated cells using a wild-type p53-specific promoter and Cre/loxP switch"Surg Today. 32. 53-58 (2002)

[文献書誌] Hosotani R, et al.: "Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice"Clin Cancer Res. 8(4). 1271-1276 (2002)

[文献書誌] Lee JU, et al.: "Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells"Eur J Cancer. 38(11). 1526-1534 (2002)

[文献書誌] Doi R, et al.: "Surgical management of intraductal papillary mucinous tumor of pancreas"Surgery. 132(1). 80-85 (2002)

[文献書誌] Wada M, et al.: "Intravenous calcium injection test is a novel complementary procedure in differential diagnosis for gastrinoma"World J Surg. 26(10). 1291-1296 (2002)

[文献書誌] Iwakura H, et al.: "Ghrelin expression in islet cell tumors : augmented expression of ghrelin in a case of glucagonoma with multiple endocrine neoplasm type I"J Clin Endocrinol Metab. 87(11). 4885-4888 (2002)

[文献書誌] Masui T, et al.: "Expression of IL-6 receptor in pancreatic cancer : involvement in VEGF induction"Anticancer Res. 22(6C). 4093-4100 (2002)

[文献書誌] Sato F, et al.: "Paratracheal lymph node metastasis is associated with cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma"Ann Surg Oncol. 9. 65-70 (2002)

[文献書誌] Nakamura Y, et al.: "High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria"Endocrine. 19(2). 127-130 (2002)

[文献書誌] Nagayama S, et al.: "Genome-wide analysis of gene expression in synovial sarcoma using a cDNA microarray"Cancer Research. 62. 5859-5866 (2002)

[文献書誌] Nagayama S, et al.: "Alterd exprsssion of the receptor and ligand in the TGFb signaling pathway in diffusely infiltrating colon carcinoma"Anti Cancer Research. 22. 3545-3554 (2002)

[文献書誌] Nakau M, et al.: "Hepatocellular carcinoma caused by loss of heterozygosity in Lkb1 gene knockout mice"Cancer Research. 62. 4549-4553 (2002)

[文献書誌] Ogawa M, et al.: "Direct electrophilic radiofluorination of a cyclic RGD peptide for in vivo αvβ3 integrin related tumor imaging"Nucl Med Biol. 30. 1-9 (2003)

[文献書誌] Tulachan S, et al.: "All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas"Diabetes. 52(1). 76-84 (2003)

[文献書誌] Shimada Y, et al.: "Cell culture in esophageal squamous cell carcinoma and the association with molecular markers"Clin Cancer Res. (in press). (2003)

[文献書誌] Imaura M: "Superficial Esophageal Neoplasm"Springer. Tokyo. 1-240 (2002)

2002 年度実績報告書

今村正之京都大学, 医学研究科, 教授 (00108995)