1997 年度実績報告書

遺伝子導入による抗癌剤感受性増強及び耐性の検討(癌遺伝子について)

研究課題

研究課題/領域番号	08671427
研究機関	福井医科大学
研究代表者	下松谷匠福井医科大学, 医学部・附属病院, 助手 (00187486)
研究分担者	堀内哲也福井医科大学, 医学部・附属病院, 助手 (20211550)
キーワード	5-fluorouracil / 癌遺伝子治療 / bystander effect / 新生血管因子 / thymidine phosphorylase / vascular endothelial growth factor / platelet derived-endothelial cell growth factor
研究概要	癌治療の新しいストラテジーの1つに、プロドラッグを活性化する酵素遺伝子を癌細胞に導入し、選択的に抗腫瘍効果を得るという方法がある。5-FUのプロドラッグであるドキシフルリジンやテガフ-ルは、thymidine phosphorylase(TP)によって5-FUに変換される。本研究では、近年TPと同一の蛋白であることが明らかとなったplatelet derived-endothelial cell growth factor(PD-ECGF)cDNAをヒト肺腺癌cell lineであるPC-9に導入し、種々の検討を行った。PD-ECGFのトランスフェクタントであるDPE2細胞のドキシフルリジン、テガフ-ルに対する感受性は、野性株のPC-9細胞と比べて、それぞれ167、26倍増強した。また、DPE2細胞を利用して、薬剤活性化遺伝子導入細胞に隣接する非導入細胞に対しても、薬剤の抗腫瘍効果が伝播するというbystander effectについての検討も行った。ドキシフルリジン10μM存在下に、DPE2細胞と野性株PC-9細胞とを1対9の割合で混合培養した場合、bystander effect陽性の結果が得られた。さらに、double chamber modelを利用して、bystander effectに細胞の接触が必要でないことが証明され、これには、培地中に遊出する5-FUが、強く関与していることも示唆された。一方、TPを新生血管因子としてとらえ、外科切除標本を対象にした検討も行った。大腸癌において、TPと癌組織内の微小血管数には、正の相関を認めた。他の新生血管因子であるVEGPと微小血管数にも正の相関が認められた。また、TP及びVEGPは、いずれも独立した予後因子となり得る事も報告した。その他、胃癌、食道癌を対象に同様の検討も行い、報告した。

研究成果
(10件)

すべてその他

すべて文献書誌 (10件)

[文献書誌] 加藤泰史: "Enhancement of drug sensitivity and a bystander effect in PC-9 cells transfected with a platelet derired endothelial cell growth factor/thymidine sphosphorylase cDNA" British Journal of Cancer. 75(4). 506-511 (1997)
[文献書誌] 谷川允彦: "Tumor angiogenesis and expression of thymidine phosphorylase/platelet derived endothelial cell growth farctor in human gastric carcinomes" Cancer Letters. 108. 281-290 (1996)
[文献書誌] 谷川允彦: "Extent of Tumor Vascularization Correlates with Prognosis and Hematogerious Metastasis in Gastric Carcinomes" Cancer Research. 56. 2671-2676 (1996)
[文献書誌] 北岡昭宏: "Improve of in Vitro Chemosensitivity Assay for Humen Solid Tumors by Application of Preculture Using Collagen Matrix" Clinical Cancer Research. 3. 295-299 (1997)
[文献書誌] 谷川允彦: "Tumor Angiogenesis and Mode of Metastasis in Patients with Colorectal Cancer" Cancer Research. 57. 1043-1046 (1997)
[文献書誌] 谷川允彦: "Association of tumour Vasculature with tumour progression and overall survival of patients with non early gastric carcinomas" British Journal of Cancer. 75(4). 566-571 (1997)
[文献書誌] 谷川允彦: "Tumor Vascularity Carrelates with the Prognosis of Patients with Esophagcal Squamons Cell Carcinome" American Cancer Society. 79(2). 220-225 (1997)
[文献書誌] 天谷博一: "Association of Vascular endothelial growth factor expression with tumor angiogenesis,survival and thymidine phosphorylase/platelet-derired endothelial cell growth factor expression in human colorectal cancer" Cancer Letters. 119. 227-235 (1997)
[文献書誌] Caide Lu: "Spontaneous Apoptosis Is Iurersely Related to Intratumoral Microvessel Density in Gastric Carcirome." Cancer Research.57. 221-224 (1997)
[文献書誌] 松村光誉司: "Platelet-derived endothelial cell growth facter/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophge infitration in colorectal cancer" Cancer Letters. (発表予定).

1997 年度 実績報告書

遺伝子導入による抗癌剤感受性増強及び耐性の検討(癌遺伝子について)

研究代表者

下松谷 匠 福井医科大学, 医学部・附属病院, 助手 (00187486)

研究成果

[文献書誌] 加藤 泰史: "Enhancement of drug sensitivity and a bystander effect in PC-9 cells transfected with a platelet derired endothelial cell growth factor/thymidine sphosphorylase cDNA" British Journal of Cancer. 75(4). 506-511 (1997)

[文献書誌] 谷川 允彦: "Tumor angiogenesis and expression of thymidine phosphorylase/platelet derived endothelial cell growth farctor in human gastric carcinomes" Cancer Letters. 108. 281-290 (1996)

[文献書誌] 谷川 允彦: "Extent of Tumor Vascularization Correlates with Prognosis and Hematogerious Metastasis in Gastric Carcinomes" Cancer Research. 56. 2671-2676 (1996)

[文献書誌] 北岡 昭宏: "Improve of in Vitro Chemosensitivity Assay for Humen Solid Tumors by Application of Preculture Using Collagen Matrix" Clinical Cancer Research. 3. 295-299 (1997)

[文献書誌] 谷川 允彦: "Tumor Angiogenesis and Mode of Metastasis in Patients with Colorectal Cancer" Cancer Research. 57. 1043-1046 (1997)

[文献書誌] 谷川 允彦: "Association of tumour Vasculature with tumour progression and overall survival of patients with non early gastric carcinomas" British Journal of Cancer. 75(4). 566-571 (1997)

[文献書誌] 谷川 允彦: "Tumor Vascularity Carrelates with the Prognosis of Patients with Esophagcal Squamons Cell Carcinome" American Cancer Society. 79(2). 220-225 (1997)

[文献書誌] 天谷 博一: "Association of Vascular endothelial growth factor expression with tumor angiogenesis,survival and thymidine phosphorylase/platelet-derired endothelial cell growth factor expression in human colorectal cancer" Cancer Letters. 119. 227-235 (1997)

[文献書誌] Caide Lu: "Spontaneous Apoptosis Is Iurersely Related to Intratumoral Microvessel Density in Gastric Carcirome." Cancer Research.57. 221-224 (1997)

[文献書誌] 松村 光誉司: "Platelet-derived endothelial cell growth facter/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophge infitration in colorectal cancer" Cancer Letters. (発表予定).

1997 年度実績報告書

下松谷匠福井医科大学, 医学部・附属病院, 助手 (00187486)

[文献書誌] 加藤泰史: "Enhancement of drug sensitivity and a bystander effect in PC-9 cells transfected with a platelet derired endothelial cell growth factor/thymidine sphosphorylase cDNA" British Journal of Cancer. 75(4). 506-511 (1997)

[文献書誌] 谷川允彦: "Tumor angiogenesis and expression of thymidine phosphorylase/platelet derived endothelial cell growth farctor in human gastric carcinomes" Cancer Letters. 108. 281-290 (1996)

[文献書誌] 谷川允彦: "Extent of Tumor Vascularization Correlates with Prognosis and Hematogerious Metastasis in Gastric Carcinomes" Cancer Research. 56. 2671-2676 (1996)

[文献書誌] 北岡昭宏: "Improve of in Vitro Chemosensitivity Assay for Humen Solid Tumors by Application of Preculture Using Collagen Matrix" Clinical Cancer Research. 3. 295-299 (1997)

[文献書誌] 谷川允彦: "Tumor Angiogenesis and Mode of Metastasis in Patients with Colorectal Cancer" Cancer Research. 57. 1043-1046 (1997)

[文献書誌] 谷川允彦: "Association of tumour Vasculature with tumour progression and overall survival of patients with non early gastric carcinomas" British Journal of Cancer. 75(4). 566-571 (1997)

[文献書誌] 谷川允彦: "Tumor Vascularity Carrelates with the Prognosis of Patients with Esophagcal Squamons Cell Carcinome" American Cancer Society. 79(2). 220-225 (1997)

[文献書誌] 天谷博一: "Association of Vascular endothelial growth factor expression with tumor angiogenesis,survival and thymidine phosphorylase/platelet-derired endothelial cell growth factor expression in human colorectal cancer" Cancer Letters. 119. 227-235 (1997)

[文献書誌] 松村光誉司: "Platelet-derived endothelial cell growth facter/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophge infitration in colorectal cancer" Cancer Letters. (発表予定).