JP2010523104A - ガン細胞検出方法ならびにガン疾患の診断およびガン疾患の処置のモニタリングのためのその使用 - Google Patents
ガン細胞検出方法ならびにガン疾患の診断およびガン疾患の処置のモニタリングのためのその使用 Download PDFInfo
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Abstract
【選択図】 図2
Description
ナノ−バイオ−チップの製造
ナノ−バイオ−チップを、標準的なマイクロシステム技術(MST)方法を使用して設計し、製造した。その構造には、小型化された電気化学的セルのアレイが含まれた。細胞がナノ体積のチャンバー(すなわち、電気化学的セル)に入れられた。この円筒状チャンバーは、それぞれが100nLの体積を保持した。すべてのアレイには、陽性および陰性の対照チャンバーが含まれた。
一般的な材料および方法
細胞株および培養:HT−29ヒト結腸ガン細胞を、ブチラート処理前の3日間、95%空気/5%CO2において37℃で、ウシ胎児血清の存在下、DMEM培地で成長させた。種々の濃度でのブチラートをHT−29細胞培養物に加えた。添加された濃度は、0mM、0.078mM、0.156mM、0.3125mM、0.625mM、1.25mM、2.5mM、5mMおよび10mMであった。最適なブチラート濃度、LC50および生存性をそれらに従って計算した。測定を、無傷の細胞を用いて、また、ガン細胞のさらなる処理(例えば、溶解)を行うことなく、PBS中で行った。
光学的測定:アルカリホスファターゼ活性を光学的基質のパラ−ニトロフェニルホスファート(直ちに使用できるPNPPキット、Sigma)により検出した。酵素による得られる生成物を420nmの波長で測定した。
本発明のバイオチップによってアッセイされたときの結腸ガン細胞に対する薬物の影響
ガン治療を各個体に合わせるために、ヒト結腸ガン細胞(HT−29)に対する様々な単一源薬物の影響を調べた。
HT−29結腸ガン細胞を様々な分化治療剤に96時間暴露し、誘導されたアルカリホスファターゼ活性を測定した。アレイ上のそれぞれの電気化学的チャンバーに、異なる薬剤(すなわち、酪酸、ブチロイルメチル−ジエチルホスファートおよびピバロイルオキシメチルブチラート)に暴露された細胞を負荷した。結果を図1A〜図1Cに示す。正常な酵素活性により、細胞が特定の薬物処理の結果として適切に分化することが示される。図1A〜図1Cに示されるように、BAおよびブチロイルメチル−ジエチルホスファートはアルカリホスファターゼの酵素活性を誘導し、一方、ピバロイルオキシメチルブチラートは酵素活性を50μM濃度の暴露において何ら誘導しなかった。このことは、HT−29ガン細胞に関するその低下した効力に関係づけられ得る[M.Entin−Meerら、Molecular Cancer Therapeutics,Vol.4,pp.1952−1961、2005;D.Engelら、Clinical Cancer Research,Vol.11,pp.9052S−9052S,2005]。加えて、陽性対照および陰性対照を行った。チャンバーに、薬物処理細胞、陰性対照としての非処理細胞、および、陽性対照としての精製アルカリホスファターゼを負荷した。ブチロイルメチル−ジエチルホスファートが、BAと類似する分化効果を発揮したが、その濃度が1.5桁ほど低下していたこと(ブチロイルメチル−ジエチルホスファートおよびBAについてそれぞれ、50μM対2.5mM)に注目することは重要である。
バイオチップによるガン細胞の定量
結果
誘導された電流シグナルと、ナノ体積チャンバーの内側で計数されたガン細胞の数との間における顕著な量相関が検出された。ガン細胞の算出結果および相対的な酵素活性が図2A〜図2Fに示される。アルカリホスファターゼ活性のモニタリングのためのアンペロメトリー応答曲線を、電気化学的アレイチップを使用して作製した。HT−29結腸ガン細胞を酪酸(2.5mM)に暴露した。基質PAPPとともにHT−29をチップ上の100nL体積の電気化学的チャンバーに入れた。電流を、220mVにおいてアンペロメトリー技術を使用して測定した。上段、中段および下段の曲線は、チャンバーの内側で計数された約100個の細胞、15個の細胞および0個の細胞の電流応答をそれぞれ表す。多数の測定により、チャンバーの内側で計数された細胞数と、アルカリホスファターゼ活性との間における大きい相関が明らかにされた。結果を図3に示す。この酵素反応を定量することができることは、電気化学的検出方法の利点と組み合わされた、チップの小型化された設計に起因する。
本発明のバイオチップによってアッセイされたときの結腸ガン細胞に対するブチロイルメチル−ジエチルホスファートの影響
バイオチップの感度をさらに調べるために、増大する数のHT−29結腸ガン細胞を異なる長さの時間にわたってブチロイルメチル−ジエチルホスファートとインキュベーションした。内因性アルカリホスファターゼの量を、本発明のバイオチップを使用して測定した。
結果を図4A〜図4C、図5A〜図5C、および、図6A〜図6Cに示す。ガン細胞に対するブチロイルメチル−ジエチルホスファートの影響は、インキュベーション時間が増大するにつれ増大した。加えて、影響の大きさが、試験された細胞の数と相関したことを認めることができる。
分化療法に対する応答でのガン細胞の高感度かつ高速大量処理可能な検出のための新しい方法が明らかにされている。ヒト結腸ガン細胞の場合において、この細胞を種々の分化療法薬物により処理し、異なる薬物に対する細胞応答を同時かつオンラインで測定した。このマイクロアレイ技術では、多数の薬物をオンラインで試験することができること、および、効果的な治療を個体に合わせることができることがもたらされる。
Claims (32)
- ガン細胞を検出する方法であって、
(a)電気的シグナルをもたらすことができる生成物を生じさせるように、酵素が細胞と基質との反応を触媒する条件のもと、細胞を酵素のための基質と接触させること;および
(b)前記電気的シグナルのレベルを測定すること
を含み、所定の閾値と比較した前記電気的シグナルのレベルの違いにより、ガン細胞が示される方法。 - 対象をガンと診断する方法であって、
(a)電気的シグナルをもたらすことができる生成物を生じさせるように、酵素が細胞と基質との反応を触媒する条件のもと、対象のサンプルにおける少なくとも1つの細胞を酵素のための基質と接触させること;および
(b)前記電気的シグナルのレベルを測定すること
を含み、所定の閾値と比較した前記電気的シグナルのレベルの違いにより、ガンが示される方法。 - ガンのための処置を個々に最適化する方法であって、
(a)対象のサンプルにおける少なくとも1つのガン細胞を少なくとも1つの抗ガン剤と接触させること;
(b)電気的シグナルをもたらすことができる生成物を生じさせるように、酵素が細胞と基質との反応を触媒する条件のもと、前記少なくとも1つのガン細胞を酵素のための基質と接触させること;および
(c)細胞によって生じた前記電気的シグナルのレベルを測定すること
を含み、前記レベルにより、前記対象のガンを処置するための前記抗ガン剤の効力が示される方法。 - 抗ガン処置を対象においてモニタリングする方法であって、
(a)少なくとも1つの抗ガン剤を対象に投与すること;および
(b)工程(a)の後での対象のサンプルにおけるガン細胞の存在またはレベルを請求項1に記載の方法に従って検出すること
を含み、前記存在またはレベルにより、ガンの状態が示される方法。 - 対象のための抗ガン処置を決定する方法であって、
(a)対象のサンプルにおけるガン細胞の存在またはレベルを請求項1に記載の方法に従って分析すること;および
(b)対象に対して、治療効果的な量の抗ガン剤を前記対象のサンプルにおける前記ガン細胞の存在またはレベルに従って投与すること
を含む方法。 - 細胞の悪性表現型を逆戻りさせることができる薬剤を同定する方法であって、
(a)少なくとも1つのガン細胞を薬剤に供すること;および
(b)細胞の悪性表現型を、工程(a)の後、および、必要な場合には工程(a)に先だって、請求項1に記載の方法に従って測定すること
を含み、表現型の逆戻りにより、細胞の悪性表現型を逆戻りさせることができる薬剤が示される方法。 - 工程(a)を工程(b)の後で繰り返すことをさらに含む、請求項5に記載の方法。
- 前記少なくとも1つの細胞は複数の細胞を含む、請求項2、3、および6のいずれかに記載の方法。
- 前記測定は、高速大量処理のための手段を使用して行われる、請求項1〜3および6のいずれかに記載の方法。
- 前記手段は、自動化サンプリングデバイス、液体取り扱い装置、ディスペンサー、電極アレイ、ロボット、または、これらの任意の組合せからなる群から選択される、請求項9に記載の方法。
- 前記接触はインビトロで行われる、請求項1に記載の方法。
- 前記接触はエクスビボで行われる、請求項1に記載の方法。
- 前記サンプルは、最大でも500個の細胞を含む、請求項2〜5のいずれかに記載の方法。
- 前記サンプルは、最小でも10個の細胞を含む、請求項2〜6のいずれかに記載の方法。
- 前記酵素はアルカリホスファターゼである、請求項1〜6のいずれかに記載の方法。
- 前記基質はp−APPである、請求項1〜6のいずれかに記載の方法。
- 前記ガン細胞は結腸ガン細胞である、請求項1〜6のいずれかに記載の方法。
- 前記測定は、電気化学的セルを使用して行われる、請求項1〜6のいずれかに記載の方法。
- 前記測定は、マルチウエルアレイ中で行われる、請求項18に記載の方法。
- 前記マルチウエルアレイの各ウエルが電気化学的セルを含む、請求項19に記載の方法。
- 前記マルチウエルアレイの各ウエルがナノ体積のウエルである、請求項19に記載の方法。
- 前記薬剤は試験組成物を含む、請求項3〜6のいずれかに記載の方法。
- 前記試験組成物は、ポリヌクレオチド、ポリペプチド、小分子化学物質、炭水化物、脂質、および、これらの組合せからなる群から選択される、請求項22に記載の方法。
- 前記薬剤は試験条件を含む、請求項3〜6のいずれかに記載の方法。
- 前記試験条件は放射線条件である、請求項24に記載の方法。
- 前記細胞は無傷である、請求項1〜3のいずれかに記載の方法。
- 前記ガン細胞は無傷である、請求項4〜6のいずれかに記載の方法。
- 前記細胞は哺乳動物細胞である、請求項1〜3のいずれかに記載の方法。
- 前記ガン細胞は哺乳動物細胞である、請求項4〜6のいずれかに記載の方法。
- ガン細胞を請求項1に記載の方法に従って検出するために構成されるシステム。
- (i)少なくとも1つの生物学的細胞を収容するために、かつ、電気化学的測定を行うために適合化された電気化学的セル;および
(ii)少なくとも1つの抗ガン剤
を含むキット。 - 前記電気化学的セルの電極におけるレドックス反応を生じさせる反応生成物をもたらすために前記生物学的細胞の酵素によって酵素反応させられる基質をさらに含む、請求項31に記載のキット。
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WO2009151783A1 (en) | 2008-04-17 | 2009-12-17 | The Neuro-Signaling Foundation | System and method to elicit apoptosis in malignant tumor cells for medical treatment |
WO2013011513A1 (en) * | 2011-07-21 | 2013-01-24 | Ramot at Tel- Aviv University Ltd. | Methods of determinig enzyme activity in preserved cell samples |
RU2489710C1 (ru) * | 2012-02-20 | 2013-08-10 | Владимир Вадимович Мошкин | Способ коммутационной хроноамперометрии |
EP2855697A1 (en) * | 2012-05-31 | 2015-04-08 | Ramot at Tel-Aviv University Ltd. | Methods and system for detecting melanoma |
KR20150074487A (ko) | 2013-12-24 | 2015-07-02 | 삼성전자주식회사 | 식각 부산물 검출 방법 및 이를 이용한 자기 저항 메모리 장치의 제조 방법 |
US11154238B2 (en) | 2015-08-07 | 2021-10-26 | Electroceuticals, Llc | Systems, methods and apparatuses for providing bioelectronic neurocode-based therapies to mammals |
CN113720893A (zh) * | 2021-09-01 | 2021-11-30 | 致慧医疗科技(上海)有限公司 | 一种基于癌细胞表面电荷强度的评估肿瘤恶性程度的方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991015595A1 (en) * | 1990-04-03 | 1991-10-17 | Oncotherapeutics | An electronic technique of identifying an effective drug for treating a cancer patient |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL154600B (nl) | 1971-02-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen. |
NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
NL154599B (nl) | 1970-12-28 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen, alsmede testverpakking. |
US3901654A (en) | 1971-06-21 | 1975-08-26 | Biological Developments | Receptor assays of biologically active compounds employing biologically specific receptors |
US3853987A (en) | 1971-09-01 | 1974-12-10 | W Dreyer | Immunological reagent and radioimmuno assay |
US3867517A (en) | 1971-12-21 | 1975-02-18 | Abbott Lab | Direct radioimmunoassay for antigens and their antibodies |
NL171930C (nl) | 1972-05-11 | 1983-06-01 | Akzo Nv | Werkwijze voor het aantonen en bepalen van haptenen, alsmede testverpakkingen. |
US3850578A (en) | 1973-03-12 | 1974-11-26 | H Mcconnell | Process for assaying for biologically active molecules |
US3935074A (en) | 1973-12-17 | 1976-01-27 | Syva Company | Antibody steric hindrance immunoassay with two antibodies |
US3996345A (en) | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4034074A (en) | 1974-09-19 | 1977-07-05 | The Board Of Trustees Of Leland Stanford Junior University | Universal reagent 2-site immunoradiometric assay using labelled anti (IgG) |
US3984533A (en) | 1975-11-13 | 1976-10-05 | General Electric Company | Electrophoretic method of detecting antigen-antibody reaction |
US4098876A (en) | 1976-10-26 | 1978-07-04 | Corning Glass Works | Reverse sandwich immunoassay |
US4879219A (en) | 1980-09-19 | 1989-11-07 | General Hospital Corporation | Immunoassay utilizing monoclonal high affinity IgM antibodies |
US5011771A (en) | 1984-04-12 | 1991-04-30 | The General Hospital Corporation | Multiepitopic immunometric assay |
US5281521A (en) | 1992-07-20 | 1994-01-25 | The Trustees Of The University Of Pennsylvania | Modified avidin-biotin technique |
US6682648B1 (en) * | 1997-08-12 | 2004-01-27 | University Of Southern California | Electrochemical reporter system for detecting analytical immunoassay and molecular biology procedures |
CN1312480C (zh) * | 2004-09-24 | 2007-04-25 | 南京大学 | 肿瘤细胞表面抗原的原位电化学免疫测定方法 |
US20060205090A1 (en) * | 2005-03-14 | 2006-09-14 | Newton Michael W | Water-soluble conjugates for electrochemical detection |
JP2010523104A (ja) * | 2007-04-02 | 2010-07-15 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッド | ガン細胞検出方法ならびにガン疾患の診断およびガン疾患の処置のモニタリングのためのその使用 |
KR101281761B1 (ko) * | 2009-03-27 | 2013-07-26 | 서강대학교산학협력단 | 전기검출기반 줄기세포 분화 측정용 센서 |
-
2008
- 2008-04-02 JP JP2010501666A patent/JP2010523104A/ja active Pending
- 2008-04-02 EP EP08720067A patent/EP2142661B1/en not_active Not-in-force
- 2008-04-02 KR KR1020097021991A patent/KR20100015774A/ko not_active Application Discontinuation
- 2008-04-02 WO PCT/IL2008/000457 patent/WO2008120216A1/en active Application Filing
- 2008-04-02 CN CN2008800182996A patent/CN101702920B/zh not_active Expired - Fee Related
-
2009
- 2009-03-05 US US12/379,974 patent/US8268577B2/en not_active Expired - Fee Related
-
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- 2012-07-18 US US13/551,642 patent/US8530179B2/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991015595A1 (en) * | 1990-04-03 | 1991-10-17 | Oncotherapeutics | An electronic technique of identifying an effective drug for treating a cancer patient |
Non-Patent Citations (2)
Title |
---|
JPN6013013160; Anal. Chem. Vol.78, 2006, pp.7625-7631 * |
JPN6013013162; Gastroenterology Vol.98,, 199005, pp.1199-1207 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015144904A (ja) * | 2015-04-20 | 2015-08-13 | 佐藤 洋 | 位置制御システム |
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CN101702920A (zh) | 2010-05-05 |
US8268577B2 (en) | 2012-09-18 |
US8530179B2 (en) | 2013-09-10 |
CN101702920B (zh) | 2013-03-13 |
US20090232740A1 (en) | 2009-09-17 |
EP2142661A1 (en) | 2010-01-13 |
US20120288877A1 (en) | 2012-11-15 |
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WO2008120216A1 (en) | 2008-10-09 |
KR20100015774A (ko) | 2010-02-12 |
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