Abstract: The present invention provides methods for obtaining genetic profiles of cancer cells in order to assess the status of a cancer in an individual. In addition, the present invention provides methods for inhibiting the growth of cancer cells that exhibit certain genetic profiles. These methods identify an important link between HER-2/neu overexpression and loss of growth inhibition by the TGF-&bgr; signaling pathway in cancer cells. Compositions as well as therapeutic and diagnostic methodologies based on this disclosure are provided.

Abstract: A novel cytokine, designated Apo-2 ligand, which induces mammalian cancer cell apoptosis is provided. The Apo-2 ligand is believed to be a member of the TNF cytokine family. Compositions including Apo-2 ligand chimeras, nucleic acid encoding Apo-2 ligand, and antibodies to Apo-2 ligand are also provided. Methods of using Apo-2 ligand to induce apoptosis and to treat pathological conditions such as cancer, are further provided.

Abstract: The invention provides methods of inducing the production of cytolytic T lymphocytes directed against malignancy or infectious agent by a mammal and treating such disease such that deleterious side effects are minimized and treatment of metastatic melanomas are surprisingly and dramatically improved.

Abstract: Apoptosis-related antigenic compounds comprising an exposed antigenic site having the amino acid sequence SEQ ID NO: 1: Glu Asp Phe Asn Leu Gly Asp Ala Leu Asp 1               5                    10 or a functionally equivalent sequence comprising at least the sequence Ala Leu Asp are disclosed.

Abstract: Apoptosis-related antigenic compounds comprising an exposed antigenic site having the amino acid sequence SEQ ID NO: 1: Glu Asp Phe Asn Leu Gly Asp Ala Leu Asp 1               5                    10 or a functionally equivalent sequence comprising at least the sequence Ala Leu Asp are disclosed.

Abstract: Although the mechanism of induction of apoptosis through antibody dependent cellular cytotoxicity (ADCC) mediated by NK cells is well understood, little is known about the fate of the reactive NK cells. Nevertheless, it has been shown that NK cells previously activated by IL-2, but not naive NK cells, died by apoptosis after Fc&ggr;RIIIa crosslinking, or after engagement in cytolytic functions. It is demonstrated that apoptosis of naive NK cells is also observed after stimulation with a rat IgG2b anti CD2 mAb (LO-CD2a/BTI-322) or anti HLAI (LO-HLA-1)mAb. The NK apoptosis is rapid (within minutes), Fas-ligand and mRNA synthesis independent and does not require a cell contact. The intracellular mechanism of NK cell apoptosis is calcium, PKC and PLA2 dependent but calcineurin and P13 kinase independent. We suggest that NK cell apoptosis results from the crosslinking on the same cell surface of CD2 or HLA-I molecules and Fc&ggr;RIIIa that exhibits a high affinity for the rat IgG2b isotype.

Abstract: The present invention relates to novel members of the Tumor Necrosis Factor family of receptors. The invention provides isolated nucleic acid molecules encoding human TR11, TR11SV1, and TR11SV2 receptors. TR11, TR11SV1, and TR11SV2 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of TR11, TR11SV1, and TR11SV2 receptor activity. The present invention further relates to antibodies that specifically bind TR11, TR11SV1, and/or TR11SV2. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of TR11, TR11SV1, and TR11SV2 receptors. Further provided are therapeutic methods for treating disease states related to aberrant proliferation and differentiation of cells which express the TR11, TR11SV1, and TR11SV2 receptors.

Abstract: The present invention encompasses methods for determining the likelihood that benign hyperplastic breast tissue or normal breast tissue adjacent to carcinoma tissue will become malignant. The methods comprise substantially isolating the tissue; and determining loss of heterozygosity (LOH) at chromosome 3p24 in the tissue. LOH at chromosome 3p24 is a prognostic indicator that the tissue may become malignant.

Abstract: A panel of biomarkers for the diagnosis and treatment of breast cancer was examined in the saliva of a cohort of 1) healthy women, 2) women with benign lesions of the breast and 3) women with diagnosed breast cancer. Recognized tumor markers c-erbB-2 (erb), cancer antigen 15-3 (CA 15-3), and tumor suppresser oncogene protein 53 (p53) were found in the saliva of all three groups of women. The levels of erb and CA 15-3 in the cancer patients evaluated, however, were significantly higher than the salivary levels of healthy controls and benign tumor patients. Conversely, pantropic p53 levels were higher in controls as compared to those women with breast cancer and those with benign tumors.

Abstract: Methods for the detection, monitoring and treatment of malignancies in which the HER-2/neu oncogene is associated are disclosed. Detection of specific T cell activation (e.g., by measuring the proliferation of T cells) in response to in vitro exposure to the HER-2/neu protein, or detection of immunocomplexes formed between the HER-2/neu protein and antibodies in body fluid, allows the diagnosis of the presence of a malignancy in which the HER-2/neu oncogene is associated. The present invention also discloses methods and compositions, including peptides, for treating such malignancies.

Abstract: An antibody that binds to a specific urogenital carcinoma tumor liberated protein (TLP) epitope, wherein the TLP comprises GlyProProGluValGlnAsnAlaAsn, is described. Also described are kits comprising the antibody, and methods of identifying TLP, and methods for diagnosing urogenital carcinoma.

Abstract: The present invention relates to novel methods and devices for detecting non-complexed prostate specific antigen (PSA), which can be used either alone or in conjunction with total PSA tests to identify patients having either benign prostatic diseases (BPD), such as benign prostatic hyperplasia, prostatitis, or glandular atrophy or prostatic adenocarcinoma (CAP). In a biological sample, one can find not only non-complexed PSA, but also PSA which has formed a complex with &agr;1-antichymotrypsin (ACT). The present invention removes or precipitates complexed PSA (PSA-ACT) and ACT from a fluid sample, thereby removing any possible interference due to the binding of complexed PSA to assay reagents.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of Xenopus CENP-E (XCENP-E), antibodies to XCENP-E, methods of screening for CENP-E modulators using biologically active CENP-E, and kits for screening for CENP-E modulators.

Abstract: Methods of predicting a propensity to developing prostate cancer are presented. The method consists of measuring the IGF status of individual. Individuals with high IGF status, as compared with normal reference range values, are at increased risk for developing prostate cancer. More particularly, the IGF status may be determined by measuring IGF-I levels and/or IGFBP-3 levels. High IGF and low IGFBP levels are indicative of a high IGF status. A method of determining the prognosis of existing prostate cancers or of monitoring disease progression involves determining the IGF/PSA status of an individual. Individuals with a high IGF/PSA status (both high IGF status and high PSA levels) tend to develop severe prostate cancer and have a poorer overall prognosis.

Abstract: More than 90% of mutations found in the p53 protein produce a conformational change in p53 which results in the exposure of an epitope, which is otherwise hidden in the hydrophobic core of the molecule. A single chain antibody (scFv) which specifically recognizes this common mutant epitope in mutant p53 but not in wild type p53 is disclosed. Also described are a DNA molecule encoding the scFv, pharmaceutical compositions comprising the antibody and methods of treatment using the pharmaceutical compositions.

Abstract: The present invention concerns the treatment of disorders characterized by the overexpression of ErbB2. More specifically, the invention concerns the treatment of human patients susceptible to or diagnosed with cancer overexpressing ErbB2 with anti-ErbB2 antibody.

Abstract: A method is disclosed for separating a polypeptide monomer from a mixture comprising dimers and/or multimers. The method comprises applying the mixture to either a cation-exchange chromatography resin or an anion-exchange chromatography resin and eluting the mixture at a gradient of about 0-1 M of an elution salt, wherein the monomer is separated from the dimers and/or multimers present in the mixture.

Abstract: An improved method of performing immunohistochemical staining on a tissue sample to determine the presence of cytoplasmic tumor marker Metallopanstimulin in cells in the tissue sample. The method consists of generally of collecting the tissue sample; fixing the tissue sample in a manner that preserves the Metallopanstimulin in the cytoplasm of the tissue cells; embedding the sample in paraffin; deparaffinizing the tissue; heating the sample to expose antigenic sites; incubating the slide with a stain blocking agent; incubating the tissue with a primary anti-Peptide A antibody having an affinity for the N-terminal portion of the Metallopanstimulin; incubating the sample with chromogen stain; rinsing the sample; dipping the slide in a counterstain; mounting the slide for reading. Materials for performing the above steps are provided in a convenient, reasonably priced kit.

Abstract: A polynucleotide molecule encoding human minor vault protein p193, or its complementary strands. A purified and isolated polynucleotide molecule consisting essentially of a nucleotide sequence encoding human minor vault protein p193, or its complementary strands, or a combination of a nucleotide sequence encoding human minor vault protein p193 and its complementary strands.

Abstract: The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a peptide from the CCK-B/gastrin-receptor conjugated to a spacer and to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B/gastrin-receptor in tumor cells, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The immunogens also comprise antibodies against the CCK-B/gastrin-receptor for passive immunization. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention.