Abstract: The invention discloses two newly-discovered Flt3 phosphorylation sites, tyrosine 589 (Tyr589) and tyrosine 591 (Tyr591) in the intracellular domain, and provides antibodies, both polyclonal and monoclonal, that selectively bind to Flt3 when phosphorylated at these novel sites. Also provided are assays utilizing these reagents, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibodies, that binds to Flt3 when phosphorylated at Tyr589 or Tyr591. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).

Abstract: A novel isolated and purified human protein inhibitor of apoptosis, termed livin, is described. A cDNA sequence which encodes the native inhibitor of apoptosis (livin) is disclosed as well as the structural coding region and the amino acid residue sequence. Molecular sequences are provided for the design and synthesis of entities that modulate biological and/or pharmacological activity of the native biomolecule. Methods are provided which employ the sequences to identify compounds that modulate biological and/or pharmacological activity of the native biomolecule. Biologically-effective antisense molecules as well as dominant negative mutant versions of the livin protein which are suitable for therapeutic are also provided. The invention is also drawn toward the study, prevention, diagnosis, and treatment of pathophysiological disorders related to apoptosis.

Abstract: Novel monoclonal antibodies and binding fragments thereof specific to human breast cancer, lung cancer, colon cancer and other cancers. The monoclonal antibody does not bind to the cell surface of normal human tissues. The corresponding cancer-specific antigen with an apparent molecular weight of 150 kd and polynucleotides encoding the antigen and the CDR regions of the antibody are Also disclosed are methods for diagnosis, prognosis and treatment of human breast cancer. The antibodies have tumor specificity and are useful for therapy, diagnosis, monitoring, detecting and imaging of cancers. The antibody-recognized cancer-specific surface antigens can serve as targets for detecting, diagnosing, inhibiting or killing cancer cells.

Abstract: An isolated nucleic acid sequence of a mitotic checkpoint gene, chfr, encodes a Chfr protein having a Forkhead-associated domain and a Ring Finger. This protein is required for regulation of the transition of cells from prophase to metaphase during mitosis. The chfr nucleic acid and Chfr polypeptide are useful in diagnosing tumorigenic cells and in screening for drugs which can inhibit the activity of Chfr in a cancer cell, thereby rendering the cell more sensitive to additional anti-tumor therapies.

Abstract: The present invention relates to a combination of peptides that may be used for treatment of cancer. The peptide combination competes for the binding of specific neuropeptides at the plasma membrane and thereby alters the levels of key intracellular molecules implicated in cell proliferation, resulting in a broad spectrum of anticancer activity. The invention also relates to pharmaceutical compositions containing a combination of such peptide analogs.

Abstract: Cancer associated antigens have been identified by autologous antibody screening of libraries of nucleic acids expressed in breast, gastric and prostate cancer cells using antisera from cancer patients. The invention relates to nucleic acids and encoded polypeptides which are cancer associated antigens expressed in patients afflicted with cancer. The invention provides, inter alia, isolated nucleic acid molecules, expression vectors containing those molecules and host cells transfected with those molecules. The invention also provides isolated proteins and peptides, antibodies to those proteins and peptides and cytotoxic T lymphocytes which recognize the proteins and peptides. Fragments of the foregoing including functional fragments and variants also are provided. Kits containing the foregoing molecules additionally are provided.

Abstract: A human nucleic acid, PD2, its encoded protein and antibodies immunologically specific thereto are disclosed herein. The expression of the disclosed PD2 gene plays a key role in the regulation of differentiation and in the maintenance of the neoplastic state. The PD2 gene and its encoded protein represent valuable therapeutic targets in the differential diagnosis and therapy of pancreatic adenocarcinomas.

Abstract: A method of inhibiting proliferation of cells associated with a tumor in a subject which comprises administering to the subject a tumor cell proliferation amount of IGF-BP3, thereby inhibiting proliferation of the cells. An improved surgical method which comprises surgically resecting a tumor from a subject and administering to the subject an amount of a protein effective to inhibit metastasis of any tumor cells released in the subject's blood circulation during the surgical resection of the tumor.

Abstract: The present invention provides a novel method for diagnosing squamous cell carcinoma or prostate cancer in a tissue sample. The method does not involve visual examination of morphology. The method comprises providing a sample from the subject and assaying for the presence, or absence or reduced level of expression of a novel gene, hereinafter referred to as the “DESC1 gene”. The method comprises isolating RNA, preferably mRNA from tissue samples, and detecting the mRNA which encodes all or part of DESC1 protein. Preferably the detection comprises amplifying the mRNA, preferably by reverse transcriptase-PCR using primers specific to a region in the DESC1 gene; and detecting the presence or absence of the amplified product to determine whether DESC1 mRNA is present or absent in the tissue sample.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.

Abstract: Methods for inhibiting angiogenesis in endothelial cells and selectively inducing apoptosis in endothelial cells via compounds which binds annexin II are provided. These compounds and methods for using these compounds are useful in the treatment of diseases or disorders characterized by unwanted angiogenesis. Also provided are pharmaceutical compositions containing a compound which binds annexin II and a pharmaceutically acceptable vehicle and methods for identifying such compounds.

Abstract: Compositions and methods involving agents that specifically bind to methylthioadenosine phosphorylase (MTAP) protein are disclosed. Illustrative compositions comprise binding agents that bind to human MTAP protein in biological samples, including embedded samples. The binding agents are useful, for example, in the detection, prognosis, and/or treatment of MTAP deficient cancers. Also disclosed are kits containing the reagents necessary for the detection of human MTAP protein in an embedded sample.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.

Abstract: The present invention relates to the discovery of novel genes encoding RIEG polypeptides. Therapeutics, diagnostics and screening assays based on these molecules are also disclosed.

Abstract: A compound comprising a target cell-specific portion and human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug, or a polynucleotide encoding said NQO2 or said variant or fragment or fusion or derivative. A recombinant polynucleotide comprising a target cell-specific promoter operably linked to a polynucleotide encoding human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug. The compounds and polynucleotides are useful in a method of treating a patient in conjunction with a suitable prodrug.

Abstract: The present invention relates to pharmaceutical compositions that include a targeting peptide, a protease specific cleavable peptide, and a chemotherapeutic drug that when conjugated are substantially inactive, but upon degradation of the cleavable sequence by a proteolytic enzyme abundant in or within the target cancer cell, the chemotherapeutic drug is released and becomes active, and to methods of use of these compositions for treatment of cancer.

Abstract: An antigen is shown to be associated with prostate cancer, and is useful for new methods and compositions for diagnosing or treating prostate cancer. This is particularly useful for individuals with prostate cancer who test negative for Prostate Specific Antigen. Additionally, this is useful for distinguishing between benign prostate disease and prostate cancer in a patient diagnosed or presenting with prostate dysfunction.

Abstract: Polypeptides whose expression is upregulated in liver tumor cells and cells from liver preneoplastic foci relative to expression in normal liver cells are disclosed as are polynucleotides that encode the polypeptides. In humans, the polynucleotide maps to a region of chromosome 15. The overexpression has also been confirmed in human liver, breast, colon and kidney cancer cell lines. It is believed that the polypeptides are overexpressed in tumor and preneoplastic cells in general.

Abstract: The invention relates to reporter molecules comprising at least one detection domain capable of emitting a signal and at least one membrane anchoring domain, which promotes the association of the reporter molecule with a membrane. The degree and rate of membrane association of the reporter molecule is approximated by the signal emitted by the detection domain. This signal provides a marker for the membrane association status of the membrane anchoring portion, or of the reporter molecule as a whole. Treatments or agents may be tested for their ability to alter membrane association or localization by observing or measuring the signal emitted by the detection domain. Thus, the invention provides means and methods for determining the capability of an agent to interfere at least in part with the distribution of a reporter molecule in a cell. These methods are useful for drug discovery; the phenotypic evaluation of cells, preferably patient cells; and for tailoring a therapeutic program for treating a patient.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.