Methods and compositions useful for diagnosis, staging, and treatment of cancers and tumors
AssigneeThe Children's Hospital of Philadelphia
InventorThomas Genetta
Life of this patent
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Abstract
Methods, compositions and kits which employ one or more ZEB specific detection reagents for detection and localization of ZEB associated molecules in tumor cells are disclosed. Also provided are methods for determining stage and progression of cancer in a mammal based on alterations in ZEB expression levels and subcellular localization. Also provided are methods for treating a cancer in a mammal by modulating ZEB expression levels and activity.
Claims29
A method of staging a tumor in a cell or tissue sample obtained from a mammal, said method comprising
- a) contacting said sample with a composition comprising one or more detection reagents selected from the group consisting of a ZEB antisense oligonucleotide and a ZEB-specific PCR primer, in an amount effective to permit detection of a ZEB encoding nucleic acid, if present, in said sample;
- b) detecting and quantifying said ZEB encoding nucleic acid in said sample;
- and
- c) determining from b) at least one of the amount and the location of said ZEB encoding nucleic acid molecule thereby staging a tumor cell or tissue sample obtained from said mammal.
A method of staging a tumor in a cell or tissue sample obtained from a mammal, said method comprising
- a) contacting said sample with a composition comprising one or more detection reagents, wherein at least one of said detection reagent is an antibody or antibody fragment having specific binding affinity for a ZEB polypeptide or fragment thereof in an amount effective to permit detection of said ZEB polypeptide or fragment thereof, if present, in said sample;
- b) detecting and quantifying said ZEB polypeptide or fragment thereof in said sample;
- and
- c) determining from b) at least one of the amount and the location of said ZEB protein, thereby staging a tumor cell or tissue sample obtained from said mammal.
A method of diagnosing a cancer or a tumor in a mammal, said method comprising
- a) obtaining a biological sample from said mammal;
- b) contacting said sample with a composition comprising one or more ZEB specific detection reagent in an amount effective to permit detection and quantitation a ZEB-associated molecule, if present, in said sample;
- c) determining from b) one or more of the amount and the sub-cellular location of said ZEB- associated molecule;
- and
- d) determining from c) altered expression levels and/or localization of said ZEB associated molecules, thereby diagnosing a cancer or a tumor in said mammal.
A method for eradicating cancer cells in a mammal comprising administering to said mammal a composition comprising a ZEB antisense oligonucleotide in an amount effective to de-repress the apoptotic pathway in a cancer cell thereby triggering the programmed cell death in said cancer cell.
A pair of ZEB-specific PCR primers comprising SEQ ID No:1 and SEQ ID No:2.
A kit for diagnosing and/or staging a tumor in a mammal, said kit comprising:
- a) a container for storing a biological sample obtained from said mammal;
- b) a composition comprising one or more ZEB-specific detection reagents in an amount effective to permit detection of a ZEB-associated molecule if present, in said sample;
- and
- c) an instructional material setting forth a protocol suitable for use in detection and quantifying said ZEB-associated molecule.
A method for eradicating cancer cells in a mammal comprising administering to said mammal a composition comprising an expression vector encoding a ZEB antisense oligonucleotide in an amount effective to de-repress the apoptotic pathway in a cancer cell thereby triggering the programmed cell death in said cancer cell.
A method for eradicating cancer cells in a mammal comprising administering to said mammal a composition comprising a dominant negative ZEB protein in an amount effective to de-repress apoptotic pathways in a cancer cell thereby triggering programmed cell death in said cancer cell.
A method for eradicating cancer cells in a mammal comprising administering to said mammal a composition comprising an expression vector encoding a dominant negative ZEB protein in an amount effective to de-repress the apoptotic pathway in a cancer cell thereby triggering the programmed cell death in said cancer cell.
An expression vector comprising nucleic acid sequences encoding an antisense ZEB molecule.
An expression vector comprising nucleic acid sequences encoding a dominant negative ZEB protein.
Dependencies are inferred from the claim text.