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WO2006034354A2 - Methodes pour le diagnostic et le traitement de tumeurs et de carcinomes a cellules renales sporadiques associes a la maladie de von hippel-lindau (vhl), d'autres tumeurs et lesions non tumorales homologues sporadiques de la maladie de vhl qui co-expriment l'epo et le recepteur de l'epo - Google Patents

Methodes pour le diagnostic et le traitement de tumeurs et de carcinomes a cellules renales sporadiques associes a la maladie de von hippel-lindau (vhl), d'autres tumeurs et lesions non tumorales homologues sporadiques de la maladie de vhl qui co-expriment l'epo et le recepteur de l'epo Download PDF

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Publication number
WO2006034354A2
WO2006034354A2 PCT/US2005/033850 US2005033850W WO2006034354A2 WO 2006034354 A2 WO2006034354 A2 WO 2006034354A2 US 2005033850 W US2005033850 W US 2005033850W WO 2006034354 A2 WO2006034354 A2 WO 2006034354A2
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WO
WIPO (PCT)
Prior art keywords
epo
epor
vhl
sporadic
tumors
Prior art date
Application number
PCT/US2005/033850
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English (en)
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WO2006034354A9 (fr
WO2006034354A3 (fr
Inventor
Zhengping Zhuang
Alexander Vortmeyer
Irina Lubensky
Edward Oldfield
Stefan Frank
Barbara Ikejiri
Tim Vogel
Youn-Soo Lee
Original Assignee
Government Of The United States Of America
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 Government Of The United States Of America filed Critical Government Of The United States Of America
Publication of WO2006034354A2 publication Critical patent/WO2006034354A2/fr
Publication of WO2006034354A9 publication Critical patent/WO2006034354A9/fr
Publication of WO2006034354A3 publication Critical patent/WO2006034354A3/fr

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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
    • G01N33/57407—Specifically defined cancers
    • G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • 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
    • G01N33/5748—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving oncogenic proteins
    • 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
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/746—Erythropoetin

Definitions

  • the methods for determining the co-expression of EPO and EPOR include a detectably labeled ligand-receptor binding assays, detectably labeled immunocytochemical assays, detectably labeled flow cytometric techniques, protein chemistry and RT-PCR.
  • Unfavorable outcome normally refers to the probability that a patient will have a relatively short lifespan due to the aggressive nature of the cancer. Patients with a less aggressive cancer or cancer that is not aggressive are expected to have a longer lifespan than a patient with an aggressive form of the cancer. EPO and EPOR Co-Expression Associated with VHL and Sporadic Renal Cell Carcinoma, Other Sporadic Counterpart Tumors and Renal Cysts:
  • oligo(dT) is used as the primer in the reverse transcription reaction. Oligo(dT) hybridizes to the poly(A) tails of mRNAs during first strand cDNA synthesis. Since all mRNAs normally have a poly(A) tail, first strand cDNA is made from all mRNAs present in the reaction (i.e., there is no specificity).
  • specific primers are used in place of oligo(dT) and specific RNAs are reverse transcribed into DNA. The specific primers preferably are complementary to a region near the 3' end of the RNA in order that full length or nearly full length cDNA is produced. Primer selection is preferably made using the guidelines described below for selection of PCR primers. A number of different primers can be used with good results. Another embodiment can be given by the use of random primers.
  • PCR Once the reverse transcriptase reaction is carried out, the cDNA produced is amplified by PCR. In one embodiment, the entire RT-PCR reaction is carried out on a standard thermal cycler according to the methods described in the GeneAmp RNA PCR kit obtained from Perkin-Elmer/Cetus, for example. A 0.5 pg sample of total RNA from the cells is used to produce the first strand cDNA.
  • the amplification cycle protocol is as follows: 95 degree C for 2 minutes, 95 degree C for 1 minute, 56 degree C for 1 minute, and 72 degree C for 2 minutes, through 35 cycles. The annealing temperature depends on the primers used.
  • a standard PCR reaction contains a buffer containing
  • PCR primers should also be chosen subject to a number of other conditions. PCR primers should be long enough (preferably 10 to 30 nucleotides in length) to minimize hybridization to greater than one region in the template. Primers with long runs of a single base should be avoided, if possible:' Primers should preferably have a percent G+C content of between 40 and 60%. If possible, the percent G+C content of the 3' end of the primer should be higher than the percent G+C content of the 5' end of the primer. Primers should not contain sequences that can hybridize to another sequence within the primer (i.e., palindromes). Two primers used in the same PCR reaction should not be able to hybridize to one another. Although PCR primers are preferably chosen subject to the recommendations above, it is not necessary that the primers conform to these conditions. Other primers may work, but have a lower chance of yielding good results.
  • the PCR procedure can also be done in such a way that the amount of PCR products can be quantified.
  • Such "quantitative PCR” procedures normally involve comparisons of the amount of PCR product produced in different PCR reactions.
  • a number of such quantitative PCR procedures, and variations thereof, are well known to those skilled in the art.
  • One inherent property of such procedures is the ability to determine relative amounts of a sequence of interest within the template that is amplified in the PCR reaction.
  • the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method, first described by Kohler and Milstein (Nature 256:495-497, 1975), in which case the hybridoma cell lines that are obtained secrete the monoclonal antibodies during growth.
  • hybridomas that ' secrete monoclonal. antibodies are made by injecting mice with the desired antigen.
  • the antigens frequently are peptide antigens which are chosen using similar procedures as described above for selection of peptide antigens for making polyclonal antibodies.
  • spleen cells are taken from the immunized mice and are fused to myeloma cells. Clones of fusion cells are then obtained and are screened for production of anti-EPO or EPOR antibodies.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Oncology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Pathology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Endocrinology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne le diagnostic de la maladie de von Hippel-Lindau (VHL) et de carcinomes à cellules rénales sporadiques, ainsi que d'autres tumeurs homologues sporadiques associées à la maladie de VHL par détection d'EPO et de récepteurs d'EPO dans lesdites tumeurs et des tissus kystiques prélevés sur des patients, en particulier sur des patients souffrant de la maladie de VHL ou présentant un risque de développer cette maladie. L'invention concerne également le traitement de patients souffrant de ces tumeurs, kystes et lésions non tumorales.
PCT/US2005/033850 2004-09-20 2005-09-20 Methodes pour le diagnostic et le traitement de tumeurs et de carcinomes a cellules renales sporadiques associes a la maladie de von hippel-lindau (vhl), d'autres tumeurs et lesions non tumorales homologues sporadiques de la maladie de vhl qui co-expriment l'epo et le recepteur de l'epo WO2006034354A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US61161604P 2004-09-20 2004-09-20
US60/611,616 2004-09-20

Publications (3)

Publication Number Publication Date
WO2006034354A2 true WO2006034354A2 (fr) 2006-03-30
WO2006034354A9 WO2006034354A9 (fr) 2006-08-24
WO2006034354A3 WO2006034354A3 (fr) 2006-10-12

Family

ID=36090654

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/033850 WO2006034354A2 (fr) 2004-09-20 2005-09-20 Methodes pour le diagnostic et le traitement de tumeurs et de carcinomes a cellules renales sporadiques associes a la maladie de von hippel-lindau (vhl), d'autres tumeurs et lesions non tumorales homologues sporadiques de la maladie de vhl qui co-expriment l'epo et le recepteur de l'epo

Country Status (1)

Country Link
WO (1) WO2006034354A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2370579A4 (fr) * 2008-12-04 2012-11-14 Traitement de maladies liées à l'érythropoïétine (epo) par inhibition d'un transcrit antisens naturel de l'epo
CN110066874A (zh) * 2019-04-26 2019-07-30 复旦大学附属华山医院 血管母细胞瘤分型诊断试剂盒

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6153407A (en) * 1992-07-28 2000-11-28 Beth Israel Deaconess Medical Center Erythropoietin DNA having modified 5' and 3' sequences and its use to prepare EPO therapeutics

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2370579A4 (fr) * 2008-12-04 2012-11-14 Traitement de maladies liées à l'érythropoïétine (epo) par inhibition d'un transcrit antisens naturel de l'epo
US8921329B2 (en) 2008-12-04 2014-12-30 Curna, Inc. Treatment of erythropoietin (EPO) related diseases by inhibition of natural antisense transcript to EPO
US10358645B2 (en) 2008-12-04 2019-07-23 Curna, Inc. Treatment of erythropoietin (EPO) related diseases by inhibition of natural antisense transcript to EPO
CN110066874A (zh) * 2019-04-26 2019-07-30 复旦大学附属华山医院 血管母细胞瘤分型诊断试剂盒

Also Published As

Publication number Publication date
WO2006034354A9 (fr) 2006-08-24
WO2006034354A3 (fr) 2006-10-12

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