JP6346202B2 - 生体液中の脱落または循環腫瘍細胞を検出するための方法 - Google Patents
生体液中の脱落または循環腫瘍細胞を検出するための方法 Download PDFInfo
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- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
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- 210000004127 vitreous body Anatomy 0.000 description 1
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
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Description
本発明は、標識下垂体アデニル酸シクラーゼ活性化ペプチド(PACAP)または血管作動性腸管ペプチド(VIP)で生体液を接触させることによって、脱落または循環腫瘍細胞を検出し、癌を診断し、生体液中の脱落または循環腫瘍細胞へのPACAPまたはVIPの結合を決定するための方法を提供する。一態様において、体液は、血液、尿または脳脊髄液である。
標識下垂体アデニル酸シクラーゼ活性化ペプチド(PACAP)は、VCAP1受容体に結合し、血液または尿中に存在する腫瘍細胞を検出し得ることを、今や見出した。標識ペプチドは、5細胞/mlの試料濃度で細胞を検出し、正確に癌細胞を同定し、混入している上皮細胞および白血球と区別し得る。腫瘍細胞の検出におけるこの標識ペプチドの使用は、容易で効率的であり、高価な機器またはトレーニングを必要としない。
PACAPペプチド、His−Ser−Asp−Gly−Ile−Phe−Thr−Asp−Ser−Tyr−Ser−Arg−Tyr−Arg−Lys−Gin−Met−Ala−Val−Lys−Lys−Tyr−Leu−Ala−Ala−Val−Leu−Aba−Lys(R)(配列番号3)は、ABI341Aペプチド合成機(Applied Biosystems, Foster City, CA)を使用して、Wang樹脂上で合成した。27−アミノ酸長PACAP配列は、その後、標準的なFmoc化学により構築され、C末端に付着した遊離スルフヒドリル基と結合した。このC末端スルフヒドリル基は、その後、TP4303を得るため、マレイミド官能化NIR色素と反応させた。
Claims (13)
- 脱落または循環腫瘍細胞を検出するための方法であって、
(a)標識を有する標識下垂体アデニル酸シクラーゼ活性化ペプチド(PACAP)または標識を有する標識血管作動性腸管ペプチド(VIP)と被験体からの生体液とを接触させること、および
(b)生体液中の脱落または循環腫瘍細胞への標識PACAPまたは標識VIPの結合を決定し、それによって脱落または循環腫瘍細胞を検出すること
を含み、ここで、
腫瘍細胞が、前立腺癌、膀胱癌、または腎臓癌からのものであり、生体液が、尿であるか、または
腫瘍細胞が、乳癌、肺癌、または卵巣癌からのものであり、生体液が、血液である、
前記方法。 - 脱落または循環腫瘍細胞が標識PACAPにより検出され、さらに、
(c)生体液中の脱落または循環腫瘍細胞への標識PACAPの結合と対照試料における標識を有する標識PACAPの結合もしくは結合の欠如またはVIPの結合とを比較すること
を含む、請求項1に記載の方法。 - 腫瘍細胞が、前立腺癌、膀胱癌、または腎臓癌からのものであり、生体液が、尿である、請求項2に記載の方法。
- 標識PACAPが、配列番号7の配列を含む、請求項3に記載の方法。
- 標識PACAPが、配列番号1、配列番号2または配列番号7のうちの1つの配列を含む、請求項1に記載の方法。
- 標識が、発色団、フルオロフォアまたはタンパク質を含む、請求項5に記載の方法。
- 標識が、発光性または蛍光性である、請求項5に記載の方法。
- 標識VIPが、配列番号3、配列番号4、配列番号5または配列番号6のうちの1つの配列を含む、請求項1に記載の方法。
- 標識PACAPまたは標識VIPの標識を視覚化して、結合を決定することをさらに含む、請求項1に記載の方法。
- 癌細胞において過剰発現される受容体に結合した標識PACAPまたは標識VIPを検出することを含む、請求項1に記載の方法。
- 標識PACAPまたは標識VIPと結合した癌細胞を標識PACAPまたは標識VIPが結合していない細胞と区別することを含む、請求項10に記載の方法。
- 標識PACAPまたは標識VIPと結合した癌細胞を標識PACAPまたは標識VIPが結合していない上皮細胞および白血球と区別することを含む、請求項10に記載の方法。
- 標識が近赤外フルオロフォアである、請求項1に記載の方法。
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US201361765329P | 2013-02-15 | 2013-02-15 | |
US61/765,329 | 2013-02-15 | ||
PCT/US2014/015758 WO2014126904A2 (en) | 2013-02-15 | 2014-02-11 | Method for detecting shed or circulating tumor cells in biological fluids |
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EP (1) | EP2956773B1 (ja) |
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KR20150143440A (ko) | 2015-12-23 |
EP2956773A2 (en) | 2015-12-23 |
US20160041170A1 (en) | 2016-02-11 |
EP2956773A4 (en) | 2016-11-23 |
WO2014126904A3 (en) | 2015-11-12 |
AU2014216517B2 (en) | 2017-04-06 |
CN105408748A (zh) | 2016-03-16 |
CN105408748B (zh) | 2019-06-04 |
CA2901246A1 (en) | 2014-08-21 |
US20240210401A1 (en) | 2024-06-27 |
HK1222450A1 (zh) | 2017-06-30 |
US20210055299A1 (en) | 2021-02-25 |
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CA2901246C (en) | 2018-12-11 |
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EP2956773B1 (en) | 2020-10-21 |
AU2014216517A1 (en) | 2015-10-08 |
WO2014126904A2 (en) | 2014-08-21 |
KR20180021253A (ko) | 2018-02-28 |
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