2003 年度実績報告書

拡散強調MRI及びMRSによる遺伝子治療の生体内効果伴定法の開発

研究課題

研究課題/領域番号	14657217
研究機関	神戸大学
研究代表者	杉村和朗神戸大学, 大学院・医学系研究科, 教授 (00136384)
研究分担者	後藤章暢神戸大学, 大学院・医学系研究科, 助教授 (70283885) 楫靖神戸大学, 医学部附属病院, 講師 (10273947) 副島俊典神戸大学, 大学院・医学系研究科, 助教授 (20231384) 佐々木良平神戸大学, 医学部附属病院, 助手 (30346267)
キーワード	遺伝子治療 / 前立腺癌 / 放射線治療 / MRI / ME spectroscopy
研究概要	我々は前立腺癌に対するアデノウイルスを用いた遺伝子治療・放射線療法の併用療法の分子機序の解明を成功させ,その成果をH13年の米国癌学会(AACR)や,H12年の米国,欧州放射線腫瘍学会(ASTRO, ESTRO)において報告してきた。それら一連の研究成果の中で,特に放射線抵抗性腫瘍に併用効果が高いことや,p53遺伝子の変異型によって遺伝子の導入効率は同じでも治療効果が異なること,放射線照射によるDNA損傷が遺伝子導入効率を著明に向上させること等,大きな3つの新知見を得てきた。今年度はさらに複数数の癌細胞腫においてp53が細胞周期停止およびアポトーシスを誘導することによって放射線照射の効果を高めることを確かめた。そして新たにp21遺伝子を導入する手法を開発し,その効果についてin vitro, in vivoでの検討を行った。正常型p21遺伝子導入によって腫瘍細胞の増殖は抑制され,これはG1期での細胞周期停止による効果であることを明らかにすると共に,in vivoにおいては正常型p21遺伝子が腫瘍細胞の生着率を低下させることを明らかにした。そしてこれらの効果はアンドロゲン依存性,非依存性腫瘍のいずれにおいても同等であった。また,これら遺伝子治療の臨床での効果評価法としてMRS撮像法も同時に開発中であるが,良好な信号を得るために必要な直腸内コイルは不快感があるためにルーチンには用いにくいという問題点がある。そこで我々はphased-arrayコイルを用いた2-Dimentional Chemical Shift Imaging (2D CSI)法と直腸内コイルを用いた場合との前立腺癌の診断能を比較し,遜色ない結果が得られることを明らかにした。今後これらを融合させ,遺伝子導入の効異について検討をする予定である。

研究成果
(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] kaji Y: "Proton two-dimensional chemical shift imaging for evaluation of prostate cancer : external surface coil vs. endorectal surface coil."J Magn Reson Imaging. 16(6). 697-706 (2002)
[文献書誌] Shirakawa T: "Messenger RNA levels and enzyme activities of 5 alpha-reductase types 1 and 2 in human benign prostatic hyperplasia (BPH) tissue."Prostate.. 58(1). 33-40 (2004)
[文献書誌] Gotoh A: "The growth inhibitory effect of p21 adenovirus on androgen-dependent and - indpendent human prostate cancer cells."BJU Int.. 92(3). 314-318 (2003)
[文献書誌] Zhang Z: "Combination with CD/5-FC gene therapy enhances killing of human bladder-cancer cells by radiation."J Gene Med. 5(10). 860-867 (2003)
[文献書誌] Hinata N: "Radiation induces p53-dependent cell apoptosis in bladder cancer cells with wild-type- p53 but not in p53-mutated bladder cancer cells."Urol Res.. 31(6). 387-396 (2003)
[文献書誌] Ohno Y: "Dynamic perfusion MRI versus per fusion scintigraphy : prediction of postoperative lung function in patients with lung cancer."AJR Am J Roentgenol. 82(1). 73-78 (2004)
[文献書誌] Mastuoka S: "Comparison of magnetic resonance imaging and ultrasonography in the prenatal diagnosis of congenitaljhoracic abnormalities."Fetal Diagn Ther. 18(6). 447-453 (2003)
[文献書誌] Ohno Y: "Clinical oxygen-enhanced magnetic resonance imaging of the lung."Top Magn Reson Imaging.. 14(3). 237-243 (2003)
[文献書誌] Ejima Y: "Combination of genistein with ionizing radiation on surviving fraction, apoptosis and cell-cycle alterations on Du-145 prostate cancer cells."Int J Radiat Oncol Biol Phys. 57(2 Suppl). S353 (2003)
[文献書誌] Yamada K: "Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma."Int J Radiat Oncol Biol Phys. 57(1). 113-119 (2003)
[文献書誌] Yamada K: "Radiotherapy for medically inoperable non-small cell lung cancer at clinical stage and II."Tumori. 89(1). 75-79 (2003)
[文献書誌] Yamada K: "Three-dimensional treatment planning using electrocardiographically gated multi-detector row CT."Int J Radial Oncol Biol Phys. 56(1). 235-239 (2003)
[文献書誌] Nishimura H: "Radiographic pulmonary and pleural changes after carbon ion irradiation."Int J Radiat Oncol Biol Phys. 55(4). 861-868 (2003)
[文献書誌] Ohno Y: "Time-resolved contrast-enhanced pulmonary MR angiography using sensitivity encoding (SENSE)."J Magn Reson Imaging. 17(3). 330-336 (2003)
[文献書誌] Takenaka D: "Differentiation of metastatic versus non-metastatic mediastinal lymph nodes in patients with non-small cell lung cancer using respiratory-triggered short inversion time inversion recovery (STIR) turbo spin-echo MR imaging."Eur J Radiol. 44(3). 216-224 (2002)
[文献書誌] Ohno Y: "MR imaging of lung cancer."Eur J Radiol. 44(3). 172-181 (2002)
[文献書誌] Yamada K: "Improvement of three-dimensional treatment planning models of small lung targets using high-speed multi-slice computed tomographic imaging."Int J Radiat Oncol Biol Phys. 54(4). 1210-1216 (2002)
[文献書誌] Hara I: "Neoadjuvant androgen withdrawal prior to external radiotherapy for locally advanced adenocarcinoma of the prostate."Int J Urol. 9(6). 322-328 (2002)
[文献書誌] Ohno Y: "Solitary pulmonary nodules : potential role of dynamic MR imaging in management initial experience."Radiology. 224(2). 503-511 (2002)
[文献書誌] Ohno Y: "Dynamic oxygen-enhanced MRI reflects diffusing capacity of the lung."Magn Reson Med. 47(6). 1139-1144 (2002)
[文献書誌] Ohno Y: "Contrast-enhanced MR per fusion imaging and MR angiography : utility for management of pulmonary arteriovenous malformations for embololherapy."Eur J Radiol. 41(2). 136-149 (2002)
[文献書誌] Yamashita T: "Images in cardiovascular medicine. Mouse coronary angiograph using synchrotron radiation microangiography."Circulation. 105(2). E3-E4 (2002)
[文献書誌] Nishimura Y: "Severe complications in advanced esophageal cancer treated with radiotherapy after intubation of esophageal stents : a questionnaire survey of the Japanese Society for Esophageal Diseases"Int J Radial Oncol Biol Phys. 56(5). 1327-1332 (2003)
[文献書誌] Sasaki R: "SUV by FDG-PET predicts outcome of non-small cell lung cancer"Int J Radial Oncol Biol Phys. 57(2 Sup). S166 (2003)
[文献書誌] Higuchi: "Regulation of the activation of nuclear factor kappaB by mitochondrial respiratory function : evidence for the reactive oxygen species-dependent and -independent pathways."Antioxid Redox Signal.
[文献書誌] "画像診断先端画像と治療-の応用"臨床医のための腹部血管造影・IVR. 168 (2002)

2003 年度 実績報告書

拡散強調MRI及びMRSによる遺伝子治療の生体内効果伴定法の開発

研究代表者

杉村 和朗 神戸大学, 大学院・医学系研究科, 教授 (00136384)

研究成果

[文献書誌] kaji Y: "Proton two-dimensional chemical shift imaging for evaluation of prostate cancer : external surface coil vs. endorectal surface coil."J Magn Reson Imaging. 16(6). 697-706 (2002)

[文献書誌] Shirakawa T: "Messenger RNA levels and enzyme activities of 5 alpha-reductase types 1 and 2 in human benign prostatic hyperplasia (BPH) tissue."Prostate.. 58(1). 33-40 (2004)

[文献書誌] Gotoh A: "The growth inhibitory effect of p21 adenovirus on androgen-dependent and - indpendent human prostate cancer cells."BJU Int.. 92(3). 314-318 (2003)

[文献書誌] Zhang Z: "Combination with CD/5-FC gene therapy enhances killing of human bladder-cancer cells by radiation."J Gene Med. 5(10). 860-867 (2003)

[文献書誌] Hinata N: "Radiation induces p53-dependent cell apoptosis in bladder cancer cells with wild-type- p53 but not in p53-mutated bladder cancer cells."Urol Res.. 31(6). 387-396 (2003)

[文献書誌] Ohno Y: "Dynamic perfusion MRI versus per fusion scintigraphy : prediction of postoperative lung function in patients with lung cancer."AJR Am J Roentgenol. 82(1). 73-78 (2004)

[文献書誌] Mastuoka S: "Comparison of magnetic resonance imaging and ultrasonography in the prenatal diagnosis of congenitaljhoracic abnormalities."Fetal Diagn Ther. 18(6). 447-453 (2003)

[文献書誌] Ohno Y: "Clinical oxygen-enhanced magnetic resonance imaging of the lung."Top Magn Reson Imaging.. 14(3). 237-243 (2003)

[文献書誌] Ejima Y: "Combination of genistein with ionizing radiation on surviving fraction, apoptosis and cell-cycle alterations on Du-145 prostate cancer cells."Int J Radiat Oncol Biol Phys. 57(2 Suppl). S353 (2003)

[文献書誌] Yamada K: "Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma."Int J Radiat Oncol Biol Phys. 57(1). 113-119 (2003)

[文献書誌] Yamada K: "Radiotherapy for medically inoperable non-small cell lung cancer at clinical stage and II."Tumori. 89(1). 75-79 (2003)

[文献書誌] Yamada K: "Three-dimensional treatment planning using electrocardiographically gated multi-detector row CT."Int J Radial Oncol Biol Phys. 56(1). 235-239 (2003)

[文献書誌] Nishimura H: "Radiographic pulmonary and pleural changes after carbon ion irradiation."Int J Radiat Oncol Biol Phys. 55(4). 861-868 (2003)

[文献書誌] Ohno Y: "Time-resolved contrast-enhanced pulmonary MR angiography using sensitivity encoding (SENSE)."J Magn Reson Imaging. 17(3). 330-336 (2003)

[文献書誌] Takenaka D: "Differentiation of metastatic versus non-metastatic mediastinal lymph nodes in patients with non-small cell lung cancer using respiratory-triggered short inversion time inversion recovery (STIR) turbo spin-echo MR imaging."Eur J Radiol. 44(3). 216-224 (2002)

[文献書誌] Ohno Y: "MR imaging of lung cancer."Eur J Radiol. 44(3). 172-181 (2002)

[文献書誌] Yamada K: "Improvement of three-dimensional treatment planning models of small lung targets using high-speed multi-slice computed tomographic imaging."Int J Radiat Oncol Biol Phys. 54(4). 1210-1216 (2002)

[文献書誌] Hara I: "Neoadjuvant androgen withdrawal prior to external radiotherapy for locally advanced adenocarcinoma of the prostate."Int J Urol. 9(6). 322-328 (2002)

[文献書誌] Ohno Y: "Solitary pulmonary nodules : potential role of dynamic MR imaging in management initial experience."Radiology. 224(2). 503-511 (2002)

[文献書誌] Ohno Y: "Dynamic oxygen-enhanced MRI reflects diffusing capacity of the lung."Magn Reson Med. 47(6). 1139-1144 (2002)

[文献書誌] Ohno Y: "Contrast-enhanced MR per fusion imaging and MR angiography : utility for management of pulmonary arteriovenous malformations for embololherapy."Eur J Radiol. 41(2). 136-149 (2002)

[文献書誌] Yamashita T: "Images in cardiovascular medicine. Mouse coronary angiograph using synchrotron radiation microangiography."Circulation. 105(2). E3-E4 (2002)

[文献書誌] Nishimura Y: "Severe complications in advanced esophageal cancer treated with radiotherapy after intubation of esophageal stents : a questionnaire survey of the Japanese Society for Esophageal Diseases"Int J Radial Oncol Biol Phys. 56(5). 1327-1332 (2003)

[文献書誌] Sasaki R: "SUV by FDG-PET predicts outcome of non-small cell lung cancer"Int J Radial Oncol Biol Phys. 57(2 Sup). S166 (2003)

[文献書誌] Higuchi: "Regulation of the activation of nuclear factor kappaB by mitochondrial respiratory function : evidence for the reactive oxygen species-dependent and -independent pathways."Antioxid Redox Signal.

[文献書誌] "画像診断先端画像と治療-の応用"臨床医のための腹部血管造影・IVR. 168 (2002)

2003 年度実績報告書

杉村和朗神戸大学, 大学院・医学系研究科, 教授 (00136384)