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Neurological Surgery No Shinkei Geka Volume 23, Issue 12 （December 1995）

Neurological Surgery 脳神経外科 23巻12号（1995年12月発行）

Japanese English

研究

ラット移植脳腫瘍に対する頸動注腫瘍壊死因子の効果—動物実験用MRIによる検索 Antitumor Effect of Intra-arterial Tumor Necrosis Factor-α in Rats with Transplanted Intracerebral Glioma and its Evaluation by MRI 原田薫雄 ^1,2 , 吉田純 ¹ , 若林俊彦 ¹ , 杉田虔一郎 ¹ , 栗栖薫 ² , 魚住徹 ² , 高橋昌哉 ³ , 山中剛 ³ Kunyu HARADA ^1,2 , Jun YOSHIDA ¹ , Toshihiko WAKABAYASHI ¹ , Kenichiro SUGITA ¹ , Kaoru KURISU ² , Tohru UOZUMI ² , B Fritz Zieroth ³ , Masaya TAKAHASHI ³ , Tsuyoshi YAMANAKA ³ ¹名古屋大学脳神経外科 ²広島大学脳神経外科 ³日本シェーリング株式会社研究部 ¹Department of Neurosurgery, Nagoya University School of Medicine ²Department of Neurosurgery, Hiroshima University School of Medicine ³NIHON SCHERING KK Research Department キーワード： Tumor necrosis factor , Glioma , Intra-arterial injection , MRI Keyword: Tumor necrosis factor , Glioma , Intra-arterial injection , MRI pp.1069-1074

発行日 1995年12月10日 Published Date 1995/12/10

DOI https://doi.org/10.11477/mf.1436901123

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Abstract 文献概要
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I．はじめに

　Tumor necrosis factor（TNF）は，主にmacrophageより産生され多面的な生理活性を有するbiological re—sponse modifierであるが，Carswellの報告以来，抗腫瘍剤として注目されている^4）．われわれは現在，臨床において悪性グリオーマ症例に対しTNF—αの頸動注療法を行っており有効例を報告しているが^24,26），投与時期，量の設定については未だ確定的な結論を得るに至っていない．今回，より有効なTNF—α投与法を検討するため，ラット移植脳腫瘍モデルを使った基礎的実験を行い，腫瘍を動物実験用MRIにより経時的に観察するとともに，組織学的検索を行ったので文献的考察を含めて報告する．

Recombinant human TNF-α was administrated intra-arterially to rats with transplanted intracerebral glioma. 1×10⁶ of T9 rat glioma cells were transplanted into Fisher 344 rat brain stereotaxically and 1000units of TNF-α was administrated at a rate of 100μl/min. via an internal carotid artery 1 or 3 weeks after the trans-plantation. The effects of TNF-α were evaluated by MRI and histopathological examinations.

Neurological symptoms, i. e. hemiparesis, appeared af-ter 9.0±0.63 days and all rats died of tumor overload-ing 14.5±0.84 days after the transplantation. Single in-jection of TNF-α on 7th day after the transplantation induced regression of the tumor size in one of six rats. The tumors were detected 3 days after transplanta-tion by MRI and they were revealed as low/iso intensi-ty mass in T1WI, iso/high intensity in T2WI, and were enhanced by Gd-DTPA heterogenously. On 7/14 days after the transplantation, the tumor grew approximately 7/10mm in diameter. The single 1000 units of TNF-α were administrated via an internal carotid artery. 3 days after the administration of TNF-α, regression of the tumor size was seen in one of six rats and decrease of peritumoral edema was seen in three. These effects of TNF-α were, however, transient and they were not demonstrated on day 7. Single injection of TNF-α was not effective for large tumors more than 10mm in dia-meter seen 14 days after the transplantation.

These data suggest that intra-arterial TNF-α should be administrated at an early stage of the tumor growth and several injections are needed to cause regression in the size of the gliomas.