JP2015519573A - 星状脳腫瘍を診断するためのシステム及び方法 - Google Patents
星状脳腫瘍を診断するためのシステム及び方法 Download PDFInfo
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Abstract
Description
共標識化:異種移植片の急性スライスは固定可能な型のSR101(Texas Redヒドラジド; Sigma)と共にインキュベーションし、室温で洗浄し、4%パラホルムアルデヒドを用いて12時間4℃で固定した。次いで、スライスをリン酸緩衝生理食塩水中ですすぎ、0.3%トリトンで透過処理し、CASブロック(Invitrogen)でブロックした(Pierreの論文参照)。GBM異種移植片スライスを抗GFAP一次抗体中で12時間インキュベーションし(Millipore; 1:500)、リンパ腫切片は抗CD20一次抗体中で12時間インキュベーションした(Millipore; 1:250)。切片は次にすすいでAlexaFluor488二次抗体(Invitrogen)と共にインキュベーションし、次いでDapi(Invitrogen)を用いて核対比染色を行った。蛍光標識された切片はvectashield(Vector labs)及びNo1.5カバースリップ(VWR)を伴うスライド上にのせた。
SR101は赤色蛍光染料であり、迅速かつ特異的に星状細胞を標識するために神経科学の研究において繰り返し使用されている。ヒト星状細胞腫細胞を同様に同定するためのこの蛍光色素分子の可能性を調べるために、本発明者らは先ずSR101を培養下のヒト星状細胞腫の細胞系U251に適用した。短インキュベーション及び蛍光オーバーレイを用いる微分干渉イメージングの後、前記蛍光色素分子は前記培養細胞の細胞質を満たし細胞核の輪郭を明確に線引きした(図1A,1B)。このことがきっかけとなり動物モデルにおける星状細胞腫細胞を標識するSR101の能力を研究することとなった。
次に本発明者らは星状細胞腫の同定に関して臨床基準である、GFAP抗体染色とSR101の染色局在性を比較した。SR101は固定には適していないので、本発明者らはこれらの実験にSR101の固定可能な型を用いた(Texas Redヒドラジド)。この蛍光色素分子の染色パターンはSR101の染色パターンに類似することは充分に確認されている。本発明者らは星状細胞腫の異種移植片由来の急性スライスを固定可能なSR101と共にインキュベーションし、前記スライスを固定し、GFAP及びDAPIを用いて対比染色を行った。
星状細胞腫のリンパ腫との確定的な術中区別は現在の臨床業務では不可能である。リンパ腫患者は切除することなく最善の治療がなされるが、星状細胞腫患者は最大の腫瘍切除で恩恵を受けるので、この差異は極めて重要である。現在、これらの腫瘍はGFAP及びCD20を用いる2段階抗体染色で臨床的に識別されている。GFAP陽性は星状細胞腫の診断を支持し、一方、CD20陽性であればリンパ腫との診断を支持する。この方法は実際に診断が出るまで典型的に最短でも24時間を要するので、手術中に情報をもたらすには遅過ぎる。
本発明者らは動物モデルにおいて星状細胞腫細胞及び反応性星状細胞を迅速に標識化し区別するためのSR101の能力を同定した後、手術中の診断薬としてのその有用性を試験した。本発明者らはSR101で標識した新鮮なヒト脳腫瘍生検を共焦点蛍光イメージングすることによって星状脳腫瘍を手術中に同定する実行可能性を決定した。本発明者らは全部で10の一般的なヒト脳腫瘍型の患者60人*からの試料をスクリーニングした。伝統的な免疫組織化学並びにパラフィン包埋ヘマトキシリン及びエオシン組織病理学により決定した診断を比較する目的で最終的な診断とした。
Claims (15)
- 星状ヒト脳腫瘍を非星状ヒト脳腫瘍と区別するための方法であって、
SR101で脳腫瘍を有する疑いのある対象由来の腫瘍組織を染色する工程、及び
星状腫瘍型か非星状腫瘍型かを確認するために蛍光画像装置を用いてSR101で染色された該組織を可視化する工程
を含む、前記方法。 - 対象由来の該腫瘍組織を生体外で染色する、請求項1記載の前記方法。
- 該非星状ヒト脳腫瘍は乏突起膠腫である、請求項1記載の前記方法。
- 該非星状ヒト脳腫瘍はCNSリンパ腫である、請求項1記載の前記方法。
- 該染色する工程及び該可視化する工程を術中に行う、請求項1記載の前記方法。
- 齧歯類の異種移植片におけるヒト神経膠腫細胞を迅速に生体内で標識化するための方法であって、
神経膠腫細胞を有する腫瘍組織を染色するために固定可能なSR101を該齧歯類に投与する工程、及び
蛍光画像装置を用いて固定可能なSR101で染色された該組織を可視化する工程
を含む、前記方法。 - 該投与する工程は動脈内注入を含む、請求項6記載の前記方法。
- 該可視化する工程は腫瘍境界の描写を含む、請求項6記載の前記方法。
- 該可視化する工程は浸潤性腫瘍細胞の描写を含む、請求項6記載の前記方法。
- 星状細胞腫の腫瘍境界を決定するための方法であって、
SR101を用いて対象由来の星状細胞腫の腫瘍組織を染色する工程、及び
該星状細胞腫と非星状細胞腫組織の間の境界を決定するために蛍光画像装置を用いて該組織を可視化する工程
を含む、前記方法。 - 対象由来の該腫瘍組織を生体外で染色する、請求項10記載の前記方法。
- 該染色する工程及び該可視化する工程は術中で行う、請求項10記載の前記方法。
- 星状ヒト脳腫瘍を非星状ヒト脳腫瘍から迅速に術中に確定するためのキットであって、
SR101を含有する氷冷した人工髄液を有する容器、
SR101を含まない氷冷した人工髄液を有する容器、及び
染色腫瘍試料を染色し画像化するための基材
を含む、前記キット。 - 前記キットは更に蛍光画像装置を含む、請求項13記載の前記キット。
- SR101を含有する該人工髄液におけるSR101の濃度は5uMである、請求項13記載の前記キット。
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US201261654438P | 2012-06-01 | 2012-06-01 | |
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PCT/US2013/043877 WO2013181655A1 (en) | 2012-06-01 | 2013-06-03 | System and method for diagnosis of astrocytic brain tumor |
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US20200254115A1 (en) | 2020-08-13 |
US10675363B2 (en) | 2020-06-09 |
JP6316803B2 (ja) | 2018-04-25 |
CA2874760C (en) | 2021-01-12 |
US20150104395A1 (en) | 2015-04-16 |
EP2856160A4 (en) | 2016-03-02 |
US11207427B2 (en) | 2021-12-28 |
CA2874760A1 (en) | 2013-12-05 |
WO2013181655A1 (en) | 2013-12-05 |
EP2856160B1 (en) | 2017-06-21 |
EP2856160A1 (en) | 2015-04-08 |
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