JP6251856B2 - バイオドシメトリパネルおよび方法 - Google Patents
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Description
本出願は、全内容が参照によって本明細書に組み入れられる、2011年9月29日に出願された米国仮特許出願第61/540,584号の利益を請求する。
本発明は、米国保健社会福祉省によって認定されたHHSO100201000009C下の連邦支援を受けて行われた。米国政府は本発明において一定の権利を有する。
(a)上記試料中の複数のバイオマーカーのレベルを測定する工程;
(b)プロセッサによって、上記試料中の上記複数のバイオマーカーの上記レベルに基づいて、上記患者における上記吸収線量を評価するためにアルゴリズムを適用する工程
を含み;上記複数のバイオマーカーは、(a)Flt−3L、G−CSF、GM−CSF、EPO、CD27、CD45、SAA、CD26、IL−12、TPO;または(b)Flt−3L、GM−CSF、SAA、TPO、CD27、CD45、CD26、IL−12を含む。
(a)上記試料中のFlt−3L、G−CSF、GM−CSF、EPO、CD27、CD45、SAA、CD26、IL−12、TPOのレベルを測定する工程;および
(b)プロセッサによって、上記試料中の上記複数のバイオマーカーの上記レベルに基づいて、上記患者における上記吸収線量を評価するためにアルゴリズムを適用する工程
を含む。
(a)患者試料中の複数のバイオマーカーのレベルを測定する工程であって、上記バイオマーカーのうちの1つまたはそれ以上のバイオマーカーは、患者における傷害の事象における正常な対照と比較して変更される、上記工程;
(b)プロセッサによって、傷害重症度指標および/または時間の関数として反応表面モデルに上記測定されたレベルを適合させる工程;
(c)上記複数のバイオマーカーを組み合わせるためにコスト関数をコンピュータ計算する工程;および
(d)既知時間間隔で上記コスト関数を最小限にする傷害重症度値を特定する工程
を含む。
(a)患者試料中の複数のバイオマーカーのレベルを測定する工程であって、上記複数のバイオマーカーのうちの1つまたはそれ以上のバイオマーカーは、放射線被曝の事象における正常な対照と比較して変更される、上記工程;
(b)プロセッサによって、放射線量または時間の関数として反応表面モデルに上記測定されたレベルを適合させる工程;
(c)上記複数のバイオマーカーを組み合わせるためにコスト関数をコンピュータ計算する工程;および
(d)既知時間間隔で上記コスト関数を最小限にする放射線量を選択する工程
を含む。
(a)傷害重症度指標または時間の関数として反応表面モデルに上記測定されたレベルを適合させる工程;
(b)上記複数のバイオマーカーを組み合わせるためにコスト関数をコンピュータ計算する工程;および
(c)既知時間間隔で上記コスト関数を最小限にする傷害重症度値を特定する工程
を含む方法によって、傷害重症度値を計算する方法を行わせるコンピュータプログラムを格納しているコンピュータ読み取り可能な記録媒体を意図する。
(a)放射線量または時間の関数として反応表面モデルに上記測定されたレベルを適合させる工程;
(b)上記複数のバイオマーカーを組み合わせるためにコスト関数をコンピュータ計算する工程;および
(c)既知時間間隔で上記コスト関数を最小限にする放射線量を選択する工程
を含む方法によって、放射線量を計算する方法を行わせるコンピュータプログラムを格納しているコンピュータ読み取り可能な記録媒体を含む。
(a)試料中の複数の血液学サロゲートバイオマーカーのレベルを測定する工程であって、該複数のバイオマーカーは、リンパ球細胞表面マーカー、好中球細胞表面マーカー、およびこれらの組み合わせを含む、上記工程;
(b)上記試料中の上記バイオマーカーの上記レベルと、正常の対照試料中の上記バイオマーカーのレベルとを比較する工程;および
(c)上記比較工程(b)に基づいて、上記末梢血白血球状態を決定する工程
を含む。
アッセイ。アッセイは、MSD MULTI−ARRAY96ウェルプレート中の多数の異なる一重化または多重化されたパネルとして開発され、MSDプレートリーダー上でECL検出を用いて分析された(例えば、Meso Scale Discoveryから市販されているプレートリーダーのSECTORまたはPR2ライン、Meso Scale Diagnostics,LLC、Gaithersburg、MDの一部門)。アッセイパネルにおいて分析されたバイオマーカーとしては、表1に列挙されるバイオマーカーが挙げられる。
マウス放射線量および複合傷害研究−個々のバイオマーカー反応。マウスの放射線量研究のためのバイオマーカー試験の結果を図1〜17に示す。それぞれの図は、それぞれの回収時間についてのバイオマーカーレベル対線量のプロット、およびそれぞれの線量についてのバイオマーカーレベル対時間のプロットを含む。パネルA〜Dにおけるマーカーについてのそれぞれのデータポイントは、EPO、IL−5、IL10、KC/GROおよびTNF−α測定を除いて、対照条件については7〜8匹のマウス全体の平均、ならびに偽条件および照射条件については10〜12匹のマウス全体の平均を表す。これらのアッセイについてのデータポイントは、対照については3〜4匹のマウス全体の平均、ならびに偽条件および照射条件については6〜8匹のマウス全体の平均を表す。また、図は、非照射対照と比較した、それぞれの条件についてのバイオマーカーレベルの変化における有意性を示すp値の表を与える。
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Claims (8)
- 患者試料における電離放射線の吸収線量または放射線誘発の組織傷害を評価するために使用される多重アッセイキットであって、前記キットは、前記試料中の複数のバイオマーカーのレベルを測定するためのアッセイチャンバおよびアッセイ試薬を含み、前記アッセイチャンバは、アレイに配置された前記アッセイ試薬を含み、前記レベルについて多重アッセイの測定を行うように構成され、前記複数のバイオマーカーは、
(a)唾液アルファ−アミラーゼ、シトルリン化タンパク質、S100B、SP−D、BPI、TSP、CA15−3、CKBB、CKMB、CKMM、FABP2、GFAP、およびNSEから選択される組織損傷バイオマーカー;
(b)Flt−3L、G−CSF、KFG、EPO、TPO、GM−CSF、およびSDF−1aから選択される組織損傷修復バイオマーカー;および
(c)CD5、CD−16b、CD20、CD177、CD26、CD27、CD40
、およびCD45から選択される血液学サロゲートマーカー
からなる群から選択される少なくとも3つのバイオマーカーを含む、上記多重アッセイキット。 - 前記複数のバイオマーカーが、バイオマーカー(a)〜(c)のうちの少なくとも4つを含む、請求項1に記載のキット。
- 請求項1に記載のキットまたは前記複数のバイオマーカーの前記レベルを測定するための、前記キットのコンポーネントを収納することができるデバイスであって、前記デバイスはコンピュータシステムと動作可能に関連し、前記コンピュータシステムは、該コンピュータシステムによって実行されるとき、コンピュータプログラムに、試料中に存在する前記複数のバイオマーカーの前記レベルを、患者によって吸収された放射線の線量と相互に関連付けることを含む方法を実行させるコンピュータプログラムを格納している、上記デバイス。
- 前記組織損傷修復バイオマーカーがFlt−3Lである、請求項1に記載のキット。
- G−CSF、EPO、GM−CSF、SDF−1a、およびこれらの組み合わせから選択される追加の組織損傷修復バイオマーカーをさらに含む、請求項1に記載のキット。
- 前記キットが、SAA、およびIL−12をさらに含む、請求項1に記載のキット。
- (a)バーコード化された患者識別タグ;(b)バーコードを含む乾燥血液スポット収集カード;(c)乾燥剤を含む試料搬送バッグ;(d)プランジャーを有するキャピラリー;または(e)ランセットを含む、追加のキットコンポーネントをさらに含む、請求項1に記載のキット。
- IL−6、CRP、SAA、IL−1、IL−5、IL−10、IL12/23、KC/GRO、IFN、IL−2、IL−4、TNF−アルファ、IL−12、IL−3、およびIL−7からなる群から選択される炎症反応バイオマーカーをさらに含む、請求項1に記載のキット。
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Cited By (6)
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JP2017138323A (ja) * | 2011-09-29 | 2017-08-10 | ウィリアム・ブレイクリー | バイオドシメトリパネルおよび方法 |
US10436784B2 (en) | 2011-09-29 | 2019-10-08 | Meso Scale Technologies, Llc | Biodosimetry panels and methods |
JP2020193983A (ja) * | 2011-09-29 | 2020-12-03 | ザ ヘンリー エム ジャクソン ファンデイション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド | バイオドシメトリパネルおよび方法 |
JP7220185B2 (ja) | 2011-09-29 | 2023-02-09 | ザ ヘンリー エム ジャクソン ファンデイション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド | バイオドシメトリパネルおよび方法 |
US11600373B2 (en) | 2011-09-29 | 2023-03-07 | Meso Scale Technologies, Llc. | Biodosimetry panels and methods |
US11967410B2 (en) | 2011-09-29 | 2024-04-23 | Meso Scale Technologies, Llc | Biodosimetry panels and methods |
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EP3511717A3 (en) | 2019-09-25 |
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EP2761294B1 (en) | 2019-02-27 |
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US20140315742A1 (en) | 2014-10-23 |
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JP2022043302A (ja) | 2022-03-15 |
JP2017138323A (ja) | 2017-08-10 |
JP2014535040A (ja) | 2014-12-25 |
US20200011866A1 (en) | 2020-01-09 |
EP2761294A1 (en) | 2014-08-06 |
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