大腸癌に対するChemo-Radio-Gene Therapyの開発

结直肠癌化疗-放射-基因疗法的发展

• 批准号: 12770690
• 负责人: 小山 文一
• 金额: $ 1.28万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12770690/
• 关键词: gene therapy; uracil phosphoribosyltransferase; 5-flvorovracil; c-Jun; radiation; Gene therapy; 5-fluorouracil

化学療法と放射線療法に遺伝子治療を応用したChemo-Radio-Gene Therapyの開発を試みた。大腸癌で発現し、放射線刺激により増強される転写因子c-Junのプロモーター領域を利用して、癌特異的放射線感受性c-Junプロモーターの開発を試みた。c-Junプロモーター制御下にlacZ遺伝子を発現するプラスミドを作製し、プロモーター活性を検討した。c-Junプロモーターの活性は、CAGプロモーター、CEAプロモーターに比して低く、放射線によるプロモーター活性増強効果は認められなかった。以上より今回作製したc-Junプロモーターは、癌特異的放射線感受性プロモーターとしての活性は低く、癌特異性と放射線感受性を兼ね備えた遺伝子発現制御機構を有するアデノウイルスベクターの開発には至らなかった。そのため、CAGプロモーター制御下に大腸菌由来uracil phosphoribosyltransferase(UPRT)遺伝子を発現するアデノウイルスベクター(AdCA-UPRT)を用いて、Chemo-Radio-Gene Therapy(AdCA-UPRT/5-FU/Radiation system)の可能性を検討した。前年度のAdCA-UPRTのヒト培養大腸癌細胞(HT29)における5-FU存在下放射線感受性増強効果に続いて、本年度は、ヌードマウス皮下腫瘍に対する抗腫瘍効果を検討した。AdCA-UPRT/5-FU/Radiadon群の抗腫瘍効果は、5-FU群、Radiation群、5FU/Radiadon群、AdCA-UPRT/5-FU群に比して有意に強力で、径8mmの皮下腫瘍をも縮小させた。以上からUPRT遺伝子を用いたChemo-Radio-Geno Therapyの有効性が示唆され、局所進行・再発大腸癌に対する新しい治療法としての可能性が示された。

Chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation method, radiation method, chemical method, radiation therapy, radiation therapy The detection of cancer and radiation line stimulation can strengthen the writing factor c-Jun. In the field of cancer detection, cancer-specific radiosensitivity c-Jun sensitivity test is carried out. In the c-Jun system, you can use the lacZ system to make sure that you are not in a position to be active. The activity of c-Jun, CAG, CEA was lower than that of normal, and the activity of radiation was higher than that of normal. The above methods have been used to detect c-Jun radiation sensitivity, radiation sensitivity, low activity, cancer-specific radiosensitivity, and cancer-specific radiosensitivity. The reason for the occurrence of the fungus is uracil phosphoribosyltransferase (UPRT), which is the origin of the fungus. It is possible to use the virus (AdCA-UPRT), Chemo-Radio-Gene Therapy (AdCA-UPRT/5-FU/Radiation system), and so on, to determine the origin of the bacteria. In the previous year, AdCA-UPRT cells were cultured in large cancer cells (HT29). There was a strong sensitivity of radiation line in 5-FU, and this year, it was reported that there was a significant increase in radiation sensitivity. AdCA-UPRT/5-FU/Radiadon group is stronger than 8mm group, 5-FU group, Radiation group, 5FU/ Radion group, AdCA-UPRT/5-FU group is smaller than that of other groups. The above UPRT drugs have been used to indicate sexual instigation by Chemo-Radio-Geno Therapy, and the possibility of further treatment of major cancer has been shown.