CN1209627C - 一种体外检测方法及用于这种方法的试剂盒 - Google Patents

一种体外检测方法及用于这种方法的试剂盒 Download PDF

Info

Publication number
CN1209627C
CN1209627C CNB998079111A CN99807911A CN1209627C CN 1209627 C CN1209627 C CN 1209627C CN B998079111 A CNB998079111 A CN B998079111A CN 99807911 A CN99807911 A CN 99807911A CN 1209627 C CN1209627 C CN 1209627C
Authority
CN
China
Prior art keywords
kit
dependent kinase
cyclin
profilin
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
CNB998079111A
Other languages
English (en)
Other versions
CN1307681A (zh
Inventor
马格努斯·冯·克内贝尔·德贝瑞茨
迪米特里·施皮科夫斯凯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Deutsches Krebsforschungszentrum DKFZ
Original Assignee
Deutsches Krebsforschungszentrum DKFZ
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Deutsches Krebsforschungszentrum DKFZ filed Critical Deutsches Krebsforschungszentrum DKFZ
Publication of CN1307681A publication Critical patent/CN1307681A/zh
Application granted granted Critical
Publication of CN1209627C publication Critical patent/CN1209627C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57411—Specifically defined cancers of cervix
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57423—Specifically defined cancers of lung

Abstract

本发明涉及癌及癌前期的早期诊断方法，包括在一机体样品中确定细胞周期调节蛋白的过表达。本发明还涉及可用于所述方法的试剂盒。

Description

一种体外检测方法及用于这种方法的试剂盒
本发明涉及癌及癌前期的早期诊断方法，特别是上呼吸道或肛殖道癌的早期诊断方法。
自50年代中期以来对大多数不同的癌已提供了预防计划。关于宫颈癌，主要是基于宫颈的细胞涂片的形态学和细胞学检查，即所谓的Pap测试，其基于妇女从20岁起定期进行的妇科学常规检查。通过细胞的形态学，涂片被分成各种强度程度的发育异常细胞变化。根据Pap I-V，这些强度程度分别代表正常、清度发育异常、稍严重发育异常、严重发育异常和浸润性癌。如果Pap测试产生令人震惊的结果，则进行小规模活组织检查并进行组织病理学检查，由此将发育异常的种类和强度确定并划分为宫颈上皮内癌(CINI-III)。
尽管有预防计划，但是每年增加400000个新病例的宫颈癌仍是妇女中发生频率为第二位的癌症。这特别是由于Pap测试结果的近30％是假阴性所致。
因此，本发明的目的是提供一种可以早期和可靠诊断宫颈癌的方法。另外，由此方法应可以区分肿瘤形成前发育异常的良性炎性改变或化生改变。
根据本发明，这可通过权利要求书中定义的本发明主题实现。
本发明基于申请人的如下观察：即细胞周期调节蛋白在许多癌，例如上呼吸道或肛殖道癌、特别是宫颈癌以及这些癌的前期中过表达。细胞周期调节蛋白的例子为细胞周期蛋白。特别提及的是调节细胞周期蛋白的细胞周期蛋白依赖性激酶，更特别提及的是调节细胞周期蛋白依赖性激酶的细胞周期蛋白依赖性激酶抑制蛋白。细胞周期蛋白依赖性激酶抑制蛋白的例子为蛋白质p14，p15，p16，p19，p21和p27。本申请人发现细胞周期调节蛋白的过表达的强度与细胞发育异常程度相关。
根据本发明，本申请人的观察用作一种癌及癌前期的早期诊断方法，其包括在一机体样品中确定细胞周期蛋白的过表达。
术语“癌及癌前期”包括任何种类和任何起源的癌及其前期。例如，它们可以是上呼吸道或肛殖道癌，特别是宫颈癌。宫颈癌中，特别提及的是其前期，例如宫颈上皮内癌(CINI-III)，原位癌(CIS)等。
术语“细胞周期调节蛋白”包括任何种类和起源的细胞周期调节蛋白。例如，这些蛋白可以是细胞周期蛋白。特别是，它们可以是调节细胞周期蛋白的细胞周期蛋白依赖性激酶。细胞周期蛋白依赖性激酶的例子是蛋白质cdk4和cdk6。更特别地，它们可以是调节细胞周期蛋白依赖性激酶的细胞周期蛋白依赖性激酶抑制蛋白。细胞周期蛋白依赖性激酶抑制蛋白的例子是蛋白质p14，p15，p16，p19，p21和p27，优选的是p16。
术语“机体样品”包括可以检测细胞周期调节蛋白的任何机体样品，这种机体样品的例子是血、涂片、痰、尿、粪便、液体(liquor)、胆汁、胃肠道分泌物、淋巴、骨髓、器官穿刺物或抽吸物和活组织检查样品。当检查肛殖道癌例如宫颈癌时，特别提及的是涂片和活检样品。
术语“确定细胞周期调节蛋白的过表达”包括适于检测细胞周期调节蛋白或其编码mRNA的表达和相应基因的扩增的任何方法。为确定过表达，显然是将待检查的机体样品与来自健康人的相应机体样品相比较，这种样品可作为标准形式存在。细胞周期调节蛋白的(过)表达可在核酸水平和蛋白质水平检测。对于蛋白质水平的检测，可以使用例如针对细胞周期调节蛋白的抗体，这些抗体可用于大多数不同方法中，如Western印迹、ELISA或免疫沉淀。有利的是抗体固定在固相载体如测试条或乳胶颗粒上。
通过本发明，可以早期诊断癌症，即在其前期诊断。
本发明的另一主题涉及进行本发明方法的试剂盒，这种试剂盒包括：
(a)检测细胞周期调节蛋白的表达的试剂，例如针对这种蛋白的抗体，或编码这种蛋白或其部分的核酸，
(b)常规助剂，如缓冲剂、载体、标记物等，和任选地
(c)用于对照反应的制剂，例如一种细胞周期调节蛋白，编码这种蛋白及其部分的核酸，或细胞制备物，例如组织切片或固定在玻片上的细胞。
以上陈述相应地适于所述试剂盒的各组分。另外，可存在各个组分的一或几个代表。
通过本发明，可以早期诊断癌，特别是可以早期诊断癌前期。还可以区分肿瘤形成前发育异常的良性炎性改变或化生改变。另一个特征是本发明方法获得的结果不进行主观评价，因而Pap测试或组织学制备的假阴性和假阳性结果可以避免。另外，本发明可以快速简便地操作，因而可用于深入筛选措施，特别是在第三世界国家中。因此，本发明对现今癌症诊断作出了重要贡献。
附图简述
图1示出在HPV16转化的宫颈癌细胞CaSki中cdk4过表达的检测。4h，8h，12h，24h是指取细胞抽提物的时间。co代表对照，arr代表加入血清。
图2示出在HPV16转化的NIH3T3细胞中cdk6和p19的过表达的检测。co代表对照。
本发明通过以下实施例解释。
实施例1在子宫颈活检样品中检测p16的过表达
(A)从20个子宫颈活检样品产生厚度为3-5微米的石蜡切片，其包括所有程度的发育异常进程，从正常组织(n＝2)经CIN I(n＝4)，II(n＝4)，III(n＝5)病变至浸润性癌(n＝5)。它们在二甲苯中脱石蜡2×10分钟并用乙醇再氢化。抗原于10mM柠檬酸盐缓冲液(pH6.0)中在高压灭菌器中于110℃、10分钟解蔽。之后用在PBS中的0.25％H2O2失活内源性过氧化物酶。用马血清(Vectastain ABC检测试剂盒，VectroLaboratories，Burlingame，美国加利福尼亚州)在室温封闭非特异性结合位点20分钟，随后切片在存在3％胎牛血清时与p16特异性单克隆抗体(Neomarkers，Fremont，美国加利福尼亚州)在室温保温45分钟。为检测p16抗体结合，加入生物素化第二抗体(马抗鼠IgG，Vectastain试剂盒，同上)保温30分钟，之后，用Vectastain试剂盒的试剂根据其指导检测结合的第二抗体，并用Mayer苏木精明矾溶液进行核心复染。
结果示出p16的过表达存在于发育异常细胞中，还示出p16过表达强度与细胞发育异常程度相关。
(B)另外，从78个子宫颈活检样品制备石蜡切片，活检样品涉及正常组织(n＝12)，CIN I(n＝15)，II(n＝14)，III(n＝18)阶段的发育异常病变及浸润性癌(n＝19)。石蜡切片如上(A)所述处理。获得表1所示数据。
                         表1
                     p16表达强度
组织学    n＝     -       +       ++      +++
正常      12      9       3
CIN I     15      10      3       2
CIN II    14      1       4       9
CIN III   18                      9       9
CxCa      19                      1       18
总计      78      20      10      21      27
由表1数据可看出，p16在发育异常和浸润性癌的细胞中过表达，过表达随着发育异常程度向浸润性癌发展而增加。
(C)另外，来自180个子宫颈癌生物活检样品的石蜡切片如上述(A)方式处理。另外，测定与上述p16特异性单克隆抗体反应的细胞百分数。在HPV阳性和HPV阴性发育异常和浸润性癌之间也进行区分，获得表2所示数据。
                       表2
              过表达p16的细胞百分数
                   n          平均百分数±标准偏差
CIN I              32         54.9±24.0
    HPV阴性        17         54.0±27.2
    HPV阳性        15         55.9±21.0
CIN II             32         70.8±18.9
    HPV阴性        14         76.0±15.8
    HPV阳性        18         66.8±20.5
CIN III            60         92.4±10.2
    HPV阴性        9          94.4±7.5
    HPV阳性        51         92.1±10.7
浸润性癌           58         97.8±5.2
    HPV阴性        5          96.4±8.1
    HPV阳性        53         97.9±4.9
表2数据显示p16在发育异常和浸润性癌的HPV阳性和HPV阴性细胞中均过表达，这一结果经正常组织的对照而证实。数据还显示与p16反应的细胞百分数随着发育异常程度向浸润性癌发展而增加。
实施例2细胞周期调节蛋白在HPV转化细胞中的过表达的检测
(A)在无血清存在下培养用HPV16转化的宫颈癌细胞CaSki，培养72小时。加入血清后，在各时间点收集细胞抽提物，进行SDS-PAGE并转移至PVDF膜(Du Pont)。用来自Santa Cruz的多克隆抗血清(1∶1000)确定cdk4的表达。另外，HPV16-E7蛋白的表达用来自Triton的抗HPV16-E7D单克隆抗体(1∶50)测定。经过氧化物酶连接的第二抗体和化学发光检测系统(NEN，Du Pont)检测各免疫应答。
结果是cdk4过表达(参见图1)。
(B)用HPV16转化NIH3T3细胞以获得HPV16-E7蛋白的表达。获得该转化细胞的细胞抽提物并如(A)所述处理。为检测cdk6和p19的表达，使用来自Santa Cruz的多克隆抗血清(1∶1000)。HPV16-E7蛋白表达的检测和各免疫应答的检测参照上述(A)所述。
结果是cdk6和p19过表达(参见图2)。

Claims (14)

1、一种用于癌及癌前期的早期诊断的试剂盒，其包含：
(a)检测细胞周期蛋白依赖性激酶抑制蛋白表达的抗体或核酸，
(b)常规助剂，和任选地
(c)用作对照的试剂。
2、权利要求1的试剂盒，其中所述常规助剂是缓冲剂、载体和/或标记物。
3、权利要求1的试剂盒，其中所述抗体是抗细胞周期蛋白依赖性激酶抑制蛋白的抗体。
4、权利要求1的试剂盒，其中所述核酸是编码细胞周期蛋白依赖性激酶抑制蛋白或其片段的核酸。
5、权利要求1-4任一项的试剂盒，其中所述试剂是一种细胞周期蛋白依赖性激酶抑制蛋白，或编码这种蛋白或其片段的核酸。
6、权利要求1-4任一项的试剂盒，其中所述试剂是一种细胞制备物或固定在玻片上的细胞。
7、在机体样品中测定细胞周期调节蛋白的过表达的体外方法，所述细胞周期调节蛋白是细胞周期蛋白依赖性激酶抑制蛋白，其中所述测定通过使用权利要求1的试剂盒进行。
8、权利要求7的方法，其中机体样品得自患有上呼吸道癌的患者。
9、权利要求7的方法，其中机体样品得自患有肛殖道癌的患者。
10、权利要求9的方法，其中机体样品得自患有宫颈癌的患者。
11、权利要求7-10任一项的方法，其中细胞周期蛋白依赖性激酶抑制蛋白是蛋白质p14、p15、p16、p18、p19、p21或p27。
12、权利要求7-10任一项的方法，其中机体样品是血、拭子、痰、尿、粪便、胆汁、骨髓、胃肠道分泌物、器官穿刺物或抽吸物、活组织检查样品和/或淋巴。
13、权利要求7-10任一项的方法，其中是在核酸水平测定过表达。
14、权利要求7-10任一项的方法其中通过抗细胞周期蛋白依赖性激酶抑制剂蛋白的抗体测定过表达。
CNB998079111A 1998-07-01 1999-07-01 一种体外检测方法及用于这种方法的试剂盒 Expired - Lifetime CN1209627C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19829473.5 1998-07-01
DE19829473A DE19829473C2 (de) 1998-07-01 1998-07-01 Verfahren zur frühen Diagnose von Carcinomen

Publications (2)

Publication Number Publication Date
CN1307681A CN1307681A (zh) 2001-08-08
CN1209627C true CN1209627C (zh) 2005-07-06

Family

ID=7872684

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB998079111A Expired - Lifetime CN1209627C (zh) 1998-07-01 1999-07-01 一种体外检测方法及用于这种方法的试剂盒

Country Status (23)

Country Link
US (2) US6709832B1 (zh)
EP (1) EP1092155B1 (zh)
JP (1) JP3404020B2 (zh)
KR (1) KR100646193B1 (zh)
CN (1) CN1209627C (zh)
AT (1) ATE230487T1 (zh)
AU (1) AU749769B2 (zh)
BR (1) BRPI9912227B8 (zh)
CA (1) CA2336153C (zh)
CZ (1) CZ292076B6 (zh)
DE (2) DE19829473C2 (zh)
DK (1) DK1092155T3 (zh)
ES (1) ES2190820T3 (zh)
HK (1) HK1038609A1 (zh)
HU (1) HUP0102744A2 (zh)
IL (1) IL140550A (zh)
MX (1) MXPA00012852A (zh)
NO (1) NO328685B1 (zh)
PL (1) PL198623B1 (zh)
RU (1) RU2217761C2 (zh)
SK (1) SK284056B6 (zh)
TR (1) TR200003903T2 (zh)
WO (1) WO2000001845A2 (zh)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7306926B2 (en) * 1998-07-01 2007-12-11 Mtm Laboratories Ag Method for detecting carcinomas in a solubilized cervical body sample
AUPP991199A0 (en) * 1999-04-21 1999-05-13 University Of Sydney, The Methods for diagnosing pre-cancerous and cancerous conditions
DE10006033B4 (de) * 2000-02-10 2005-11-10 Professor Dr. Magnus von Knebel Doeberitz Chirurgische Universitätsklinik Sektion für Molekulare Diagnostik und Therapie Immunisierung eines Individuums gegen Carcinome und ihre Vorstufen
US20060057651A1 (en) * 2000-12-08 2006-03-16 Bowdish Katherine S Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof
US7408041B2 (en) 2000-12-08 2008-08-05 Alexion Pharmaceuticals, Inc. Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof
US9249229B2 (en) 2000-12-08 2016-02-02 Alexion Pharmaceuticals, Inc. Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof
AUPR201500A0 (en) * 2000-12-11 2001-01-11 Biosceptre Pty Ltd Methods for identifying pre-neoplastic and neoplastic states in mammals
DE10063179A1 (de) * 2000-12-18 2002-06-20 Bayer Ag Verfahren zur spezifischen Detektion von Tumorzellen und ihren Vorstufen in Gebärmutterhalsabstrichen durch simultane Messung von mindestens zwei verschiedenen molekularen Markern
DE60230482D1 (de) * 2001-01-17 2009-02-05 Intreat Pty Ltd Antikörper gegen nichtfunktionelle p 2 x 7 rezeptoren, diagnose und behandlung von krebs und anderen leiden
EP1369694A1 (en) 2002-04-09 2003-12-10 MTM Laboratories AG Method for discrimination of metaplasias from neoplastic or preneoplastic lesions
DK1388734T3 (da) * 2002-08-01 2004-05-03 Mtm Lab Ag Metode til opløsningsbaseret diagnose
EP1422526A1 (en) * 2002-10-28 2004-05-26 MTM Laboratories AG Method for improved diagnosis of dysplasias
US20050266409A1 (en) * 2003-02-04 2005-12-01 Wyeth Compositions and methods for diagnosing, preventing, and treating cancers
WO2004076686A1 (ja) * 2003-02-26 2004-09-10 Sysmex Corporation 細胞の検査方法
ATE289685T1 (de) * 2003-08-25 2005-03-15 Mtm Lab Ag Verfahren zum nachweis von karzinomen in solubilisierten zervikalen körperproben
KR20110027823A (ko) * 2004-03-24 2011-03-16 트리패스 이미징, 인코포레이티드 자궁경부 질환의 검사 방법 및 조성물
WO2005116241A1 (ja) * 2004-05-31 2005-12-08 Sysmex Corporation 哺乳動物細胞の性質判定方法及びこれを用いた癌の診断方法
EP1628135A1 (en) * 2004-08-20 2006-02-22 MTM Laboratories AG Method for detecting medically relevant conditions in a solubilized LBC sample
US7892750B1 (en) * 2004-12-23 2011-02-22 University Of Notre Dame Du Lac Cathepsin E as a marker of colon cancer
JP4766969B2 (ja) 2005-09-14 2011-09-07 シスメックス株式会社 組織性質判定装置
US7972776B2 (en) * 2005-11-15 2011-07-05 Oncohealth Corporation Protein chips for HPV detection
KR20140091765A (ko) 2006-01-12 2014-07-22 알렉시온 파마슈티칼스, 인코포레이티드 Ｏｘ-2/ｃｄ200에 대한 항체 및 이들의 용도
JP2010505426A (ja) * 2006-10-10 2010-02-25 バイオスセプター インターナショナル リミテッド 非機能性ｐ２ｘ７受容体に対する抗体を産生するハイブリドーマ
US20100003704A1 (en) * 2008-06-13 2010-01-07 Shuling Cheng IN SITU detection of early stages and late stages HPV infection
US8968995B2 (en) * 2008-11-12 2015-03-03 Oncohealth Corp. Detection, screening, and diagnosis of HPV-associated cancers
JP5111902B2 (ja) * 2007-03-14 2013-01-09 シスメックス株式会社 癌の診断支援装置
US8921114B2 (en) 2007-08-24 2014-12-30 Sysmex Corporation Diagnosis support system for cancer, diagnosis support information providing method for cancer, and computer program product
NZ583894A (en) 2007-09-14 2013-01-25 Biosceptre Int Ltd Antibodies that bind to a non atp binding p2x7 receptor
AU2008299594B2 (en) 2007-09-14 2013-10-03 Biosceptre International Limited Purinergic (P2X) receptors in extra-cellular body fluid
CA2729868C (en) * 2008-07-04 2018-07-10 Biosceptre International Limited Anti- p2x7 peptides and epitopes
JP2012526286A (ja) * 2009-05-07 2012-10-25 オンコヘルス コーポレーション ヒトパピローマウイルス（ｈｐｖ）およびｈｐｖ関連癌の初期段階および後期段階の検出、スクリーニング、および診断のための高度または≧ｃｉｎ２の同定
EP2966090B1 (en) 2009-08-20 2018-10-10 Biosceptre (Aust) Pty Ltd Anti p2x7 receptor antibodies and fragments thereof
ES2667003T3 (es) 2009-12-24 2018-05-09 Biosceptre (Aust) Pty Ltd Anticuerpos para receptores P2X7 oligoméricos no funcionales
CN102822672B (zh) 2010-01-08 2015-12-09 安科健康公司 用于诊断和筛选与hpv有关的癌症的高通量细胞基hpv免疫测定
US8900813B2 (en) 2010-08-17 2014-12-02 Medical Diagnostic Laboratories, Llc CIP2A as a biomarker in detection of cervical cancer
EP2613808B1 (en) 2010-09-10 2017-11-08 Biosceptre (Aust) Pty Ltd Companion animal cancer treatments with an anti p2x7 antibody
US9551700B2 (en) 2010-12-20 2017-01-24 Milagen, Inc. Device and methods for the detection of cervical disease
CA2840251C (en) 2011-07-01 2023-09-12 Biosceptre International Limited Combination therapy of diseases that are associated with non-functional p2x7 receptor expression
WO2013067268A1 (en) 2011-11-03 2013-05-10 Tripath Imaging, Inc. Methods and compositions for preparing samples for immunostaining
JP6174035B2 (ja) 2011-11-15 2017-08-02 ユニヴァーシティ・オヴ・マイアミ ヒトパピローマウイルスを検出し頭頸部扁平上皮癌を予後予測する方法
US11761963B2 (en) 2017-09-27 2023-09-19 Alexion Pharmaceuticals, Inc. Biomarker signature for predicting tumor response to anti-CD200 therapy
WO2019234176A1 (en) 2018-06-07 2019-12-12 Universitaet Des Saarlandes Novel biomarkers for carcinoma diagnosis
CN108893534A (zh) * 2018-06-26 2018-11-27 华中科技大学鄂州工业技术研究院 泛癌症诊断标记物
RU2707884C1 (ru) * 2018-10-03 2019-12-02 федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет) (ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Се Способ ранней диагностики почечно-клеточной карциномы по наличию антител к зрительному аррестину
FR3088640A1 (fr) 2018-10-14 2020-05-22 Smart Diagnostix Pharma Nouveau polypeptide se liant specifiquement a la proteine p16
CN111257565A (zh) * 2018-12-03 2020-06-09 上海细胞治疗集团有限公司 一种衰老细胞的检测试剂盒及其检测方法
CN113295683A (zh) * 2021-05-24 2021-08-24 烟台海关技术中心 过氧化苯甲酰检测方法

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4281061A (en) * 1979-07-27 1981-07-28 Syva Company Double antibody for enhanced sensitivity in immunoassay
US5268463A (en) * 1986-11-11 1993-12-07 Jefferson Richard A Plant promoter α-glucuronidase gene construct
DE69333043T2 (de) 1992-10-16 2004-05-06 Cold Spring Harbor Laboratory Umlagerung des cyclin komlexes und seine darauf bezogenen anwendungen
AU5694694A (en) * 1992-12-02 1994-06-22 Denis F. Hochstrasser A method for detecting growing cells using translationally controlled tumor protein p21
US5543291A (en) * 1993-01-29 1996-08-06 Dana Farber Cancer Institute Method of detecting carcinoma
US6316208B1 (en) * 1994-01-07 2001-11-13 Memorial Sloan-Kettering Cancer Center Methods for determining isolated p27 protein levels and uses thereof
AU685627B2 (en) * 1994-03-18 1998-01-22 Myriad Genetics, Inc. Germline mutations in the MTS gene and method for detecting predisposition to cancer at the MTS gene
US5763190A (en) * 1994-09-21 1998-06-09 The Trustees Of The University Of Pennsylvania Methods for the identification of compounds capable of inducing the nuclear translocation of a receptor complex comprising the glucocoticoid receptor type II and viral protein R interacting protein
US6033847A (en) * 1995-02-06 2000-03-07 St. Jude Children's Research Hospital InK4c-p18 and InK4d-p19, inhibitors of cyclin-dependent kinases CDK4 and CDK6, and uses thereof
US5976799A (en) 1996-03-21 1999-11-02 The Board Of Trustees Of The University Of Arkansas Early detection of ovarian carcinoma using P16 gene products
US5851797A (en) * 1996-06-19 1998-12-22 Regeneron Pharmaceuticals, Inc. Tie ligand-3, methods of making and uses thereof
US5858683A (en) * 1996-08-30 1999-01-12 Matritech, Inc. Methods and compositions for the detection of cervical cancer
WO2000024245A1 (en) * 1998-10-28 2000-05-04 President And Fellows Of Harvard College REGULATION OF TH2 CELL ACTIVITY BY MODULATION OF NFATp AND NFAT4 ACTIVITY

Also Published As

Publication number Publication date
EP1092155B1 (de) 2003-01-02
SK20312000A3 (sk) 2001-10-08
DE19829473C2 (de) 2000-08-10
CA2336153C (en) 2005-12-20
JP3404020B2 (ja) 2003-05-06
WO2000001845B1 (de) 2000-04-20
DE19829473A1 (de) 2000-01-13
KR20010074632A (ko) 2001-08-04
PL198623B1 (pl) 2008-07-31
DK1092155T3 (da) 2003-03-24
IL140550A (en) 2005-08-31
NO328685B1 (no) 2010-04-26
WO2000001845A3 (de) 2000-02-17
SK284056B6 (sk) 2004-08-03
CZ20004922A3 (cs) 2001-07-11
PL345407A1 (en) 2001-12-17
BRPI9912227A (pt) 2001-04-24
NO20006681D0 (no) 2000-12-28
US20030152993A1 (en) 2003-08-14
AU5848799A (en) 2000-01-24
MXPA00012852A (es) 2003-09-11
CZ292076B6 (cs) 2003-07-16
TR200003903T2 (tr) 2001-06-21
NO20006681L (no) 2001-02-26
HK1038609A1 (en) 2002-03-22
CN1307681A (zh) 2001-08-08
JP2002519681A (ja) 2002-07-02
HUP0102744A2 (hu) 2001-11-28
ATE230487T1 (de) 2003-01-15
ES2190820T3 (es) 2003-08-16
DE59903915D1 (de) 2003-02-06
RU2217761C2 (ru) 2003-11-27
WO2000001845A2 (de) 2000-01-13
IL140550A0 (en) 2002-02-10
KR100646193B1 (ko) 2006-11-17
EP1092155A2 (de) 2001-04-18
AU749769B2 (en) 2002-07-04
BRPI9912227B8 (pt) 2021-07-06
CA2336153A1 (en) 2000-01-13
BRPI9912227B1 (pt) 2013-08-20
US6709832B1 (en) 2004-03-23

Similar Documents

Publication Publication Date Title
CN1209627C (zh) 一种体外检测方法及用于这种方法的试剂盒
RU2315312C2 (ru) Способ диагностики на основе раствора
Arnouk et al. Characterization of molecular markers indicative of cervical cancer progression
Viswanathan et al. Insulinoma-associated protein 1 is a sensitive and specific marker for lung neuroendocrine tumors in cytologic and surgical specimens
JP2017133831A (ja) 大腸がんの転移検出方法
US20120309015A1 (en) Methods and compositions for detecting endometrial or ovarian cancer
Igoh et al. Identification and evaluation of potential forensic marker proteins in vaginal fluid by liquid chromatography/mass spectrometry
CN105899673B (zh) 作为子宫颈癌和存活期的生物标记物的角蛋白
US8133736B2 (en) Methods for detecting or monitoring cancer using LPE as a marker
Song et al. Correlation of p16 immunostaining in cell‐blocks with corresponding tissue specimens for squamous cell carcinomas of the oropharynx
CN115436640B (zh) 适于可评估甲状腺结节恶性程度或概率的多肽的替代基质
KR102384848B1 (ko) 방광암용 바이오마커로서의 케라틴 17
CN114460297A (zh) 一种用于检测血液中循环前列腺上皮细胞的免疫荧光试剂盒及其使用方法
Leung et al. Triaging abnormal cervical cancer screening tests using p16INK4a detection by ELISA on fresh cervical samples
KR102370435B1 (ko) 유방암의 아형 분류에 사용되는 단백질의 질량분석기 기반 정량 방법 및 그 용도
JP5872285B2 (ja) 腎がん血中マーカー
Didier et al. Cervical Intra-Epithelial Neoplasia: Index of Papillomavirus Infection and Histopathological Grade in Lubumbashi Patients
CN112698033A (zh) 一种血源性外泌体her2的检测方法及其应用
CN117907596A (zh) 一种乳腺癌早期诊断标志物、试剂盒及其应用
CN112362874A (zh) 一种宫颈癌筛查试剂盒
KR101825644B1 (ko) Nedd4-1 단백질의 발현 수준을 측정하는 물질을 포함하는 자궁경부암 진단용 조성물 및 이를 이용한 자궁경부암 진단을 위한 정보제공방법
CN117805377A (zh) 尿液fbp1作为糖尿病肾病疾病进展标志物的应用
CN112684173A (zh) 一种her2的检测方法及其应用
CN117169503A (zh) Serpina10作为分子标志物在制备用于诊断前列腺癌的产品中的应用
TWI487913B (zh) A method for finding serum / plasma biomarker molecules of hepatocellular carcinoma and a method for detecting serum / plasma biomarker molecules

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CX01 Expiry of patent term

Granted publication date: 20050706

CX01 Expiry of patent term