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EP0931262A1 - Marqueurs biochimiques de l'endometre humain - Google Patents

Marqueurs biochimiques de l'endometre humain

Info

Publication number
EP0931262A1
EP0931262A1 EP97939048A EP97939048A EP0931262A1 EP 0931262 A1 EP0931262 A1 EP 0931262A1 EP 97939048 A EP97939048 A EP 97939048A EP 97939048 A EP97939048 A EP 97939048A EP 0931262 A1 EP0931262 A1 EP 0931262A1
Authority
EP
European Patent Office
Prior art keywords
leu
ala
glu
gly
lys
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.)
Withdrawn
Application number
EP97939048A
Other languages
German (de)
English (en)
Inventor
Inger Byrjalsen
Peter Mose Larsen
Stephen John Fey
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.)
Immunodiagnostic Systems Nordic AS
Original Assignee
Osteometer Biotech AS
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
Priority claimed from GBGB9618600.2A external-priority patent/GB9618600D0/en
Priority claimed from GBGB9707132.8A external-priority patent/GB9707132D0/en
Application filed by Osteometer Biotech AS filed Critical Osteometer Biotech AS
Publication of EP0931262A1 publication Critical patent/EP0931262A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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
    • G01N33/57442—Specifically defined cancers of the uterus and endometrial
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/689—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to pregnancy or the gonads
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/36—Gynecology or obstetrics

Definitions

  • the endometrium is the mucous lining of the uterine cavity.
  • the endometrium is the organ in the body that shows the greatest changes under the influence of the sex hormones, oestradiol and progesterone.
  • the endometrium proliferates until progesterone from the corpus luteum transforms the oestrogen-primed proliferative endometrium to a secretory phase endometrium. In due course this is followed by shedding of the fully transformed endometrium during the menstruation, and a new cycle will begin.
  • endometrial status is assessed by histological and biochemical analysis of endometrial biopsies. This is time-consuming, expensive and causes discomfort for the woman. It would be highly desirable to identify biochemical markers which could be measured in body fluids reflecting the endometrial status, obviating the need for endometrial biopsies . The detection of such markers in histological samples would also however be advantageous as an additional method of recognising the histological status of such samples .
  • references to the proteins herein include references to modified forms of the proteins and derivatives of the proteins, including but not restricted to glycosylated, phosphorylated, acetylated, methylated or lipidated forms thereof.
  • the invention provides a method of characterising a biological sample comprising detecting or quantitating therein one or more proteins produced by the endometrium in increased amounts in hyperplasia or in adenocarcinoma as shown by 2D gel electrophoresis comparison of cell lysates of endometrial biopsies from normal endometrium and endometrium showing hyperplasia or adenocarcinoma, excluding variations due to the menstrual cycle, or detecting or quantitating a fragment or breakdown product thereof, or a nucleic acid coding therefor, or an antibody thereto.
  • Said protein, fragment, breakdown product, antibody or nucleic acid may preferably be detected in a body fluid sample but may also be detailed in other forms of sample such as histological samples or cytological samples .
  • the invention includes an immunological binding partner specifically reactive with a protein as defined above with a fragment or breakdown product thereof or with a nucelic acid coding therefor.
  • the invention includes also an assay kit for use m such an analysis method comprising an immunological binding partner as described.
  • This aspect of the invention has resulted from studies aiming to detect endometrial proteins with increased synthesis in endometrial adenocarcinoma as compared to the synthesis during the normal menstrual cycle; to detect endometrial proteins with increased synthesis in endometrial hyperplasia as compared to the synthesis during the normal menstrual cycle; and to detect proteins showing a cycle-related expression during the normal menstrual cycle.
  • the invention relates to the discovery of markers of the "proliferative" phase of the human endometrium.
  • a protein marker for the "secretory" phase of the endometrium has been previously described, see US-A-4 , 489, 166. No similar marker has been described for the proliferative phase although certain candidate proteins were described in Ref . 1.
  • the human endometrium Under influence of the sex hormones, oestradiol and progesterone, the human endometrium undergoes cyclical variation with an oestrogen-dominated phase, i.e. the proliferative phase, an ovulation phase, i.e. the interval phase, a progesterone-dominated phase, i.e. the secretory phase, and finally the endometrium is shed, i.e. the menstrual phase.
  • an oestrogen-dominated phase i.e. the proliferative phase
  • an ovulation phase i.e. the interval phase
  • a progesterone-dominated phase i.e. the secretory phase
  • the endometrium is shed, i.e. the menstrual phase.
  • the same cyclical variation of the endometrium is seen in postmenopausal women receiving sequentially combined hormone replacement therapy.
  • a method of characterising a biological sample comprising detecting or quantitating therein one or more proteins produced by the endometrium in increased amounts during the proliferative phase of the endometrium as shown in 2D gel elctrophoresis comparison of cell lysates of endometrial biopsies from normal endometrium in its proliferative and secretory phases and characterised by one of the following combinations of molecular weight and pi values : -
  • Such a method may preferably be for detecting the phase of the endometrium.
  • This aspect of the invention includes a method of determining the proliferative/secretory phase status of the endometrium comprising the quantitative or qualitative measurement in a sample of any one or more of the proteins defined above or a breakdown product or fragment thereof . It also includes an immunological binding partner for any of the said proteins, breakdown products or fragments or a cell line producing such a binding partner.
  • the sequences and properties of proteins discussed above relate to human proteins, the assay procedures of the invention may be practised on samples arising from other species.
  • references to proteins herein should be understood to include proteins having a degree of homology of at least 60% with the given amino acid sequences irrespective of any modifications of said amino acids.
  • modified amino acids such as phosphorylated, acetylated, amidated, methylated, glycosylated or lipidated derivatives of an amino acid should thus be considered to be the same as the amino acid without any such modification.
  • modified amino acids such as phosphorylated, acetylated, amidated, methylated, glycosylated or lipidated derivatives of an amino acid should thus be considered to be the same as the amino acid without any such modification.
  • Such peptides may be derived from similar proteins from other species, e.g. other mammals such as mouse, rabbit, guinea pig, pig, or cow or may be entirely or predominantly of synthetic origin.
  • the degree of homology may be advantageously be at least 65%, or at least 70%. Under certain circumstances, it is advantageous that the degree of homology is even higher such as at least 80% or at least 90%.
  • Other DNA sequences which encode substantially the same amino acid sequence as a gene encoding a marker protein, i.e. a marker gene may be used in the practice of the present invention. These include, but are not limited to, allelic genes and homologous genes from other species.
  • Nucleic acid fragments comprising a nucleotide sequence which codes for a protein described above or a peptide derived from it as well as nucleic acid fragments which hybridise with these nucleic acid fragments or a part thereof under stringent hybridisation conditions, e.g. 5 mM monovalent ions (O.lxSSC), neutral pH and 65°C are important aspects of the invention.
  • stringent hybridisation conditions e.g. 5 mM monovalent ions (O.lxSSC), neutral pH and 65°C are important aspects of the invention.
  • the term "highly stringent”, when used in conjunction with hybrisidation conditions, is as defined in the art, i.e. 5-10°C under the melting point T m , cf, Sambrook et al, 1989, pages 11.45 - 11.49.
  • nucleic acid is meant a polynucleotide of high molecular weight which can occur as either DNA or RNA and may be either single-stranded or double-stranded.
  • the invention relates to a binding means which specifically binds to a relevant protein or peptide or nucleic acid fragment as described above.
  • the invention relates to an antibody which specifically binds to a relevant protein or peptide or an antigen-binding fragment thereof, i.e. a polyclonal antibody, a monoclonal antibody, chimeric antibody, single chain antibody fragment, Fab and Fab' fragments, and an Fab expression library.
  • both monoclonal and polyclonal antibodies will be useful in providing the basis for one or more assays to detect relevant peptides and proteins.
  • Antibodies which are directed against epitopes that are specific for the proteins will be most useful as cross reaction will be minimised therewith.
  • assay methods and kits may be produced according to standard methodology.
  • the proteins may be obtained in purified form, either by extraction from tissues or by synthesis, and antibodies may be raised thereto or to characterising peptide sequences thereof. Standard assay formats employing such antibodies may be utilised according to the invention.
  • immunoassays are contemplated as including various types of enzyme linked immunoassays (ELISA) , immunoblot techniques, and the like, known in the art. However, it is readily appreciated that utility is not limited to such assays, and useful embodiments including RIAs and other non-enzyme linked antibody binding assays or procedures.
  • ELISA enzyme linked immunoassays
  • the proteins themselves or peptides derived from the protein sequences may be used in detecting auto- antibodies to such proteins.
  • Figure 1 Fluorograph of a two-dimensional gel electrophoresis of [ 35 S]meth ⁇ on ⁇ ne labelled endometrial proteins separated in the first dimension by ISO- elect ⁇ c focusing (IEF; pi 3.5-7) and in the second dimension by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The locations of the spots with increased synthesis in hyperplasia are indicated.
  • Figure 2 Fluorograph of a two-dimensional gel electrophoresis of [ 35 S]meth ⁇ omne labelled endometrial proteins separated in the first dimension by non- equilib ⁇ um pH gradient gel electrophoresis (NEPHGE; pi 6.5-11) and in the second dimension by sodium dodecyl sulphate polyacrylamide gel electrophoresis . The locations of the spots with increased synthesis in hyperplasia are indicated.
  • NEPHGE non- equilib ⁇ um pH gradient gel electrophoresis
  • Figure 3 Fluorograph of a two-dimensional gel electrophoresis of [ 35 S] metmonine labelled endometrial proteins separated in the first dimension oy ISO- elect ⁇ c focusing (IEF; pi 3.5-7) and in the second dimension by sodium dodecyl sulphate polyacrylamide gel elctrophoresis . The locations of the spots with increased synthesis in adenocarcinoma are indicated.
  • Figure 4 Fluorograph of a two-dimensional gel electrophoresis of [ 35 S]meth ⁇ on ⁇ ne labelled endometrial proteins separated m the first dimension by non- equilibnum pH gradient gel electrophoresis (NEPHGE; pi 6.5-11) and in the second dimension by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The locations of the spots with increased synthesis in adenocarcinoma are indicated.
  • NEPHGE non- equilibnum pH gradient gel electrophoresis
  • Figure 5 Fluorograph of a two-dimensional gel electrophoresis of [ 35 S3meth ⁇ on ⁇ ne labelled endometrial proteins separated in the first dimension by ISO- elect ⁇ c focusing (IEF; pi 3.5-7) and in the second dimension by sodium dodecyl sulphate polyacrylamide gel elctrophoresis. The locations of the spots with increased synthesis in proliferative phase endometrium are indicated.
  • Figure 6 Fluorograph of a two-dimensional gel electrophoresis of [ 35 S]meth ⁇ on ⁇ ne labelled endometrial proteins separated in the first dimension by non- equilibrium pH gradient gel electrophoresis (NEPHGE; pi 6.5-11) and in the second dimension by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The locations of the spots with increased synthesis in proliferative phase endometrium are indicated.
  • Figure 7 Tryptic digestion mass spectroscopic characteristics of I#350. The peaks marked with a star are not protein identification specific but represents methodologically non-specific peaks.
  • Figure 8 Tryptic digestion mass spectroscopic characteristics of I#687.
  • the peaks marked with a star are not protein identification specific but represents methodologically non-specific peaks.
  • Figure 9 Tryptic digestion mass spectroscopic characteristics of N#414.
  • the peaks marked with a star are not protein identification specific but represents methodologically non-specific peaks.
  • Figure 10 Tryptic digestion mass spectroscopic characteristics of I#1035. The peaks marked with a star are not protein identification specific but represents methodologically non-specific peaks.
  • Figure 11 Tryptic digestion mass spectroscopic characteristics of N#26. The peaks marked with a star are not protein identification specific but represents methodologically non-specific peaks.
  • Figure 12 Tryptic digestion mass spectroscopic charac- teristics of N#31+N#32. The peaks marked with a star are not protein identification specific but represents methodologically non-specific peaks.
  • endometrial samples were obtained as follows.
  • the proteins of the endometrial biopsies were metabolically labelled with "s-methionine for 20 hours, and total cell lysates were processed for 2D gel electrophoresis, a technique in which proteins are separated in the first dimension according to the isoelectric point and in the second dimension according to the molecular weight. It was possible to study proteins with iso-electric points ranging from 3.5 to 11 and relative molecular weights ranging from 10 to 300 kDa. After electrophoresis the gels were fixed and treated for fluorography . The fluorograms of the 2D gel electrophoresis were subjected to quantitative analysis by computer-aided analysis, by which the density of each spot was quantified, the fluorogram patterns were matched i.e. numbers were assigned to each spot and the same spot was given the same number on all the fluorograms. The density
  • menstrual cycle-related proteins so identified have been identified by amino acid sequence analysis (Ref.2). Selected menstrual cycle-related proteins were excised from several 2D gels, concentrated by ID sodium dodecylsulphate polyacrylamide gel electro- horesis, and cleaved in situ by trypsin. The tryptic fragments were extracted and separated by reverse phase high pressure liquid chromatography. Finally, the partial amino- terminal amino acid sequence of selected tryptic fragments were determined for each protein. For identification the amino acid sequences of the tryptic fragments were compared to previously reported sequences by searching in databases . The hyperplasia and adenocarcinoma associated proteins of the present invention may be sequenced and further characterised by similar methods.
  • spots had increased expression in both hyperplasia and adenocarcinoma. Based on subjective evaluation, preferred subgroups of spots were selected with increased synthesis in hyperplasia and in adenocarcinoma, respectively. The preferred subgroup of spots with increased synthesis in hyperplasia were selected as being the spots showing the highest relative increase in expression in hyperplasia as compared to the samples obtained from women during the normal mentrual cycle and women with irregular proliferative phase endometrium.
  • the preferred subgroup of spots with increased synthesis in adenocarcinoma were selected as the spots showing the highest relative increase in expression in adenocarcinoma as compared to the samples obtained from women during the normal menstrual cycle and women with irregular proliferative phase endometrium.
  • the preferred subgroup of 7 spots with increased synthesis in hyperplasia is given in Table 3
  • the preferred subgroup of 12 spots with increased synthesis in adenocarcinoma is given in Table
  • the information obtained from the 2D-gel electrophoresis with respect to the isoelectric point (pi) and the molecular weight (MW) of a preferred subgroup of these spots which show increased synthesis in proliferative phase endometrium are given in Table 5 and their positions are indicated in Figures 5 and 6.
  • Protein ID ' Accession Identification in protein or nucleotide databases (e.g. SwissProt, Protein Identification Resource (PIR) or EMBL)
  • the proteins of interest may be isolated from endometrial tissue or other protein sources by 2D gel electrophoresis or by using chromatographic techniques. Poly- or monoclonal antibodies towards the protein of interest can be raised, and immunoassays can be established based on such antibodies. Synthetic peptides being fragments characteristic of such proteins may be used for the same purposes . Assays may be based on more than one such protein for measurement at one time.
  • MOLECULE TYPE protein
  • HYPOTHETICAL NO
  • MOLECULE TYPE protein
  • HYPOTHETICAL NO
  • MOLECULE TYPE protein
  • HYPOTHETICAL NO

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Reproductive Health (AREA)
  • Oncology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biophysics (AREA)
  • Hospice & Palliative Care (AREA)
  • Genetics & Genomics (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention porte sur des procédés relatifs à des essais de détection ou de quantification de l'une des protéines spécifiquement produites par l'endomètre en association avec l'hyperplasie, l'adénocarcinome, ou les phases proliférantes de l'endomètre. Les protéines concernées ont été identifiées par électrophorèse sur gel 2D avec identification subséquente par prise au spectre de masse des empreintes des produits de digestion de la trypsine.
EP97939048A 1996-09-06 1997-09-05 Marqueurs biochimiques de l'endometre humain Withdrawn EP0931262A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB9618600 1996-09-06
GBGB9618600.2A GB9618600D0 (en) 1996-09-06 1996-09-06 Biochemical markers of the human endometrium
GBGB9707132.8A GB9707132D0 (en) 1997-04-08 1997-04-08 Biochemical markers of the human endometrium
GB9707132 1997-04-08
PCT/GB1997/002394 WO1998010291A1 (fr) 1996-09-06 1997-09-05 Marqueurs biochimiques de l'endometre humain

Publications (1)

Publication Number Publication Date
EP0931262A1 true EP0931262A1 (fr) 1999-07-28

Family

ID=26309984

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97939048A Withdrawn EP0931262A1 (fr) 1996-09-06 1997-09-05 Marqueurs biochimiques de l'endometre humain

Country Status (5)

Country Link
EP (1) EP0931262A1 (fr)
JP (1) JP2001501300A (fr)
AU (1) AU4127597A (fr)
CA (1) CA2265470A1 (fr)
WO (1) WO1998010291A1 (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6033869A (en) * 1997-03-20 2000-03-07 Incyte Pharmaceuticals, Inc. Polynucleotide encoding a novel human cytokine/steroid receptor
DE19824230A1 (de) * 1998-05-29 1999-12-02 Starzinski Powitz Anna Neues Endometriose-assoziiertes Gen
JP2002535658A (ja) * 1999-01-25 2002-10-22 プロクレア・バイオサイエンスィズ・インコーポレーテッド 子宮内膜症診断のための方法およびキット
US6743595B1 (en) 1999-01-25 2004-06-01 Metriogene Biosciences Inc. Method and diagnostic kit for diagnosis of endometriosis
GB0017716D0 (en) * 2000-07-19 2000-09-06 Osteometer Biotech As Biochemical markers of the human endometrium
US7504222B2 (en) 2001-10-31 2009-03-17 Millennium Pharmaceuticals, Inc. Compositions, kits, and methods for identification, assessment, prevention, and therapy of breast cancer
US20050100967A1 (en) * 2003-07-11 2005-05-12 Science & Technology Corporation @ Unm Detection of endometrial pathology
US20070275871A1 (en) * 2003-08-28 2007-11-29 Biorexis Technology, Inc. Epo Mimetic Peptides and Fusion Proteins
ATE476525T1 (de) * 2003-12-23 2010-08-15 Mount Sinai Hospital Corp Verfahren zum nachweis von mit endometrialer krankheit oder phase assoziierten markern
EP1767944A1 (fr) * 2005-09-26 2007-03-28 ProteoSys AG mPR phosphorylé ou non-phosphorylé comme marqueur diagnostique ou comme cible thérapeutique
BRPI0710884A2 (pt) * 2006-04-24 2011-08-16 Shantha West Inc polipeptìdeo isolado, ácido nucléico, célula transformada, vetor, composição farmacêutica, kit, e, métodos para identificar uma célula que expressa um polipeptìdeo, de triagem para um distúrbio proliferativo da célula, para induzir ou aumentar uma resposta imune a um polipeptìdeo, para tratar um indivìduo tendo, ou em risco de ter, um tumor, para identificar um inibidor ou estimulador da expressão de um polipeptìdeo, e para triar um indivìduo tendo, ou em risco de ter, um distúrbio proliferativo da célula
EP2067040A2 (fr) * 2006-09-26 2009-06-10 ProteoSys AG Utilisation d'au moins une isoforme du composant 1 de la membrane du recepteur de la progesterone (pgrmc1)
EP1906185A1 (fr) * 2006-09-26 2008-04-02 ProteoSys AG Utilisation d'au moins un isoforme de composant 1 récepteur membranaire de la progestérone (PGRMC1)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994028021A1 (fr) * 1993-05-28 1994-12-08 Medical University Of South Carolina Proteines endometriales, compositions antigeniques et procedes de detection de l'endometriose

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9810291A1 *

Also Published As

Publication number Publication date
AU4127597A (en) 1998-03-26
JP2001501300A (ja) 2001-01-30
WO1998010291A1 (fr) 1998-03-12
CA2265470A1 (fr) 1998-03-12

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