WO1998014469A3 - An epithelial protein and dna thereof for use in early cancer detection - Google Patents

An epithelial protein and dna thereof for use in early cancer detection Download PDF

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Publication number
WO1998014469A3
WO1998014469A3 PCT/US1997/017714 US9717714W WO9814469A3 WO 1998014469 A3 WO1998014469 A3 WO 1998014469A3 US 9717714 W US9717714 W US 9717714W WO 9814469 A3 WO9814469 A3 WO 9814469A3
Authority
WO
WIPO (PCT)
Prior art keywords
epithelial
protein
epithelial protein
precancer
hnrnp
Prior art date
Application number
PCT/US1997/017714
Other languages
French (fr)
Other versions
WO1998014469A2 (en
Inventor
James L Mulshine
Melvyn S Tockman
Original Assignee
Us Health
Univ Johns Hopkins
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 US08/725,027 external-priority patent/US6251586B1/en
Application filed by Us Health, Univ Johns Hopkins filed Critical Us Health
Priority to AU46635/97A priority Critical patent/AU4663597A/en
Publication of WO1998014469A2 publication Critical patent/WO1998014469A2/en
Publication of WO1998014469A3 publication Critical patent/WO1998014469A3/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4747Apoptosis related proteins
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/112Disease subtyping, staging or classification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Wood Science & Technology (AREA)
  • Immunology (AREA)
  • Hospice & Palliative Care (AREA)
  • Oncology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Toxicology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

The present invention is a purified and isolated epithelial protein, peptide and variants thereof whose increased presence in an epithelial cell is indicative of precancer. One epithelial protein which is an early detection marked for lung cancer was purified from two human lung cancer cell lines, NCI-H720 and NCI-H157. Using a six-step procedure, the epithelial protein was purified using a Western blot detection system under both non-reducing and reducing conditions. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C18 HPLC and analytic C4 HPLC. After an approximately 25,000 fold purification the immunostaining protein was > 90 % pure as judged by coomassie blue staining after reducing SDS-PAGE. The primary epithelial protein share some sequence homology with the heterogeneous nuclear ribonucleoprotein (hnRNP) A2. A minor co-purifying epithelial protein shares some sequence homology with the splice variant hnRNP-B1. Molecular analysis of primary normal bronchial epithelial cell cultures demonstrated a low level the epithelial protein expression, consistent with immunohistochemical staining of clinical samples, and an increased level of expression in most lung cancer cells. The epithelial protein is a marker of epithelial transformation in lung, breast, bone, ovary, prostate, kidney, melanoma and myeloma and may be casual in the process of carcinogenesis. Methods are provided for monitoring the expression of the epithelial protein, peptides and variants using molecular and immunological techniques as a screen for precancer and cancer in mammals. A method of computerized diagnoses of cancer and precancer is provided which detects levels of hnRNP messenger RNA.
PCT/US1997/017714 1996-10-02 1997-10-02 An epithelial protein and dna thereof for use in early cancer detection WO1998014469A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU46635/97A AU4663597A (en) 1996-10-02 1997-10-02 An epithelial protein and dna thereof for use in early cancer detection

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/725,027 US6251586B1 (en) 1995-10-02 1996-10-02 Epithelial protein and DNA thereof for use in early cancer detection
US08/725,027 1996-10-02

Publications (2)

Publication Number Publication Date
WO1998014469A2 WO1998014469A2 (en) 1998-04-09
WO1998014469A3 true WO1998014469A3 (en) 1998-05-28

Family

ID=24912843

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/017714 WO1998014469A2 (en) 1996-10-02 1997-10-02 An epithelial protein and dna thereof for use in early cancer detection

Country Status (2)

Country Link
AU (1) AU4663597A (en)
WO (1) WO1998014469A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060094105A1 (en) 1998-04-24 2006-05-04 University Hospitals Of Cleveland Mixed cell diagnostic systems for detection of respiratory, herpes and enteric viruses
WO2001021649A2 (en) * 1999-09-22 2001-03-29 Cedars-Sinai Medical Center Nucleic acids encoding vitamin d response element binding proteins, products related thereto, and methods of using same
US7435588B2 (en) * 2005-09-20 2008-10-14 Diagnostic Hybrids, Inc. Systems for detection and production of respiratory, herpes and enteric viruses
EP2204380A1 (en) * 2008-12-23 2010-07-07 Charité-Universitätsmedizin Berlin hnRNP A3 related peptides and use thereof for diagnosis of rheumatoid arthritis

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997012975A1 (en) * 1995-10-02 1997-04-10 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services An epithelial protein and dna thereof for use in early cancer detection

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997012975A1 (en) * 1995-10-02 1997-04-10 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services An epithelial protein and dna thereof for use in early cancer detection

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BIAMONTI G ET AL: "Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1", NUCLEIC ACIDS RESEARCH, vol. 22, no. 11, 1994, OXFORD GB, pages 1996 - 2002, XP002024996 *
BURD CG: "Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: A diversity of RNA binding proteins is generated by small peptide inserts", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 86, 1989, WASHINGTON US, pages 9788 - 9792, XP002024995 *
MULSHINE JL ET AL: "Monoclonal antibodies that distinguish non-small cell from small cell lung cancer.", J IMMUNOL, JUL 1983, 131 (1) P497-502, UNITED STATES, XP000616367 *
TOCKMAN MS ET AL: "Considerations in bringing a cancer biomarker to clinical application.", CANCER RES, MAY 1 1992, 52 (9 SUPPL) P2711S-2718S, UNITED STATES, XP000614974 *
TOCKMAN MS ET AL: "The early detection of second primary lung cancers by sputum immunostaining. LCEWDG Investigators. Lung Cancer Early Detection Group.", CHEST, DEC 1994, 106 (6 SUPPL) P385S-390S, UNITED STATES, XP000614983 *
ZHOU J ET AL: "Purification and characterization of a protein that permits early detection of lung cancer. Identification of heterogeneous nuclear ribonucleoprotein-A2/B1 as the antigen for monoclonal antibody 703D4.", J BIOL CHEM, MAY 3 1996, 271 (18) P10760-6, UNITED STATES, XP000616365 *

Also Published As

Publication number Publication date
WO1998014469A2 (en) 1998-04-09
AU4663597A (en) 1998-04-24

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