Abstract: The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human breast cancer predisposing gene (BRCA2), some mutant alleles of which cause susceptibility to cancer, in particular breast cancer. More specifically, the invention relates to germline mutations in the BRCA2 gene and their use in the diagnosis of predisposition to breast cancer. The present invention further relates to somatic mutations in the BRCA2 gene in human breast cancer and their use in the diagnosis and prognosis of human breast cancer. Additionally, the invention relates to somatic mutations in the BRCA2 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the BRCA2 gene, including gene therapy, protein replacement therapy and protein mimetics.

Abstract: The present invention is based on the purification and sequencing of isozymes of plasma hyaluronidase (pHAse) found in urine. Specifically, urine contains two hyaluronidases (HAses): 1) a 57 kDa HAse that is apparently the same as the 57 kDa HAse found in plasma; and 2) a 45 kDa HAse, which is found in urine but not plasma. The smaller urine isozyme is composed of two disulfide-linked polypeptides produced by endoproteolytic cleavage of the 57 kDa isoform. The present invention thus features a urinary hyaluronidase (uHAse) polypeptide and nucleotide sequences encoding a Chain A polypeptide and a Chain B polypeptide, the two polypeptides of which uHAse is composed. In a particular aspect, the uHAse is a human uHAse (huHAse), preferably a huHAse composed of the Chain A and B polypeptides having SEQ ID NOS: 2 and 4, respectively. In related aspects the invention features polynucleotide sequence encoding Chain A and Chain B polypeptides, preferably having the sequences of SEQ ID NOS: 1 and 3, respectively.

Abstract: A method of treating liver cancer involving administration to the subject a therapeutically effective amount of a bombesin analog.

Abstract: A drug comprising either a peptide having the LH-RH action or an LH-RH antagonist is carried on an intrauterine contraceptive device (IUD) so as to be able to provide controlled release. Once the IUD is put in the uterus, the carried drug is gradually released over such a prolonged period of treatment time as, for example, several months to be continuously absorbed through the uterus mucosa or the vagina mucosa. This construction makes it possible to reduce the patient's pain and such a troublesomeness as frequent drug administration and continuously administer a necessary drug over a prolonged period of time while taking a contraceptive measures.

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: The present invention relates to immunogenic complexes of heat shock proteins (hsp) noncovalently bound to exogenous antigenic molecules which when administered to an individual elicit specific immunological responses in the host. Methods of prevention and treatment of cancer and infectious disease are provided.

Abstract: A gene, mcl-1, of the bcl-2 family is disclosed along with its nucleotide and amino acid sequence. Also disclosed are diagnostic and therapeutic methods of utilizing the mcl-1 nucleotide and polypeptide sequences.

Abstract: The invention relates to a method for inducing bone formation via administration of an extract of devitalized, freeze dried Saos-2 cells. The extract is prepared by contacting the freeze dried Saos-2 cells, which are devitalized in the act of freeze drying, with a weak denaturing agent of the type used to separate proteins from cells. The extract does have properties superior to comparable treatment using whole Saos-2 cells. The extract is then further treated by applying it to a removing separating gel, and then fractions from the gel which have a molecular weight of from about 10 kd to about 60 kd. Also described are the extract itself, and formulations containing it.

Abstract: A new family of tumor rejection antigen precursors, and the nucleic acid molecules which code for them, are disclosed. These tumor rejection antigen precursors are referred to as DAGE tumor rejection antigen precursors, and the nucleic acid molecules which code for them are referred to as GAGE coding molecules. Various diagnostic and therapeutic uses of the coding sequences and the tumor rejection antigens, and their precursor molecules are described.

Abstract: The invention relates to a method for inducing bone formation via administration of an extract of devitalized, freeze dried Saos-2 cells. The extract is prepared by contacting the freeze dried Saos-2 cells, which are devitalized in the act of freeze drying, with a weak denaturing agent of the type used to separate proteins from cells. It is not clear that the active ingredient in the extract is a protein; however, the extract does have properties superior to comparable treatment using whole Saos-2 cells. Also, described are the extracts themselves and various compositions containing it.

Abstract: The present invention relates to methods of preparing a purified non-covalent heat shock protein 70-peptide complex capable of eliciting an immune response in a mammal comprising purifying heat shock protein 70-peptide complexes from mammalian tumor cells or mammalian cells infected with a virus, bacteria, or other infectious agent in the absence of ATP.

Abstract: The present invention provides the methods to isolate the proteins specifically induced apoptosis (programmed cell death) in prostate cancer cells (LNCAP), leukemia cells (HL-60), and breast cancer cells (MCF-70), but without effect in normal human lung fibroblast cells (CCD 39 Lu). P-1 has no effect on breast cancer cells. Five proteins have been isolated from the conditioned media of culture cells: (1) Apogen P-1: the proteins (Apogen P-1a, Apogen P-1b and Apogen P-1c) isolated from the conditioned medium of XC cells are able to induce apoptosis in prostate cancer cells (LNCAP) without effect in normal human lung fibroblast (CCD 39 Lu), colon cancer (T84), breast cancer (MCF-7) and leukemia (HL-60) cells. (2) Apogen P-2: the protein isolated from the conditioned medium of C3H10T1/2 cells is able to induce apoptosis in prostate cancer cells (LNCAP) and breast cancer (MCF-7) without effect in normal human lung fibroblast (CCD 39 Lu) and colon cancer (T84) cells.

Abstract: A method for inducing or enhancing in a human subject the production of antibodies reactive with the polypeptide subunit of Urinary Tumor Associated Antigen having a molecular weight of about 90 to 100 kD after reduction by .beta.-mercaptoethanol and separation by SDS-polyacrylamide gel electrophoresis is disclosed. The method comprises administering to the subject an effective dose of a composition comprising inactivated tumor cells having Urinary Tumor Associated Antigen on the cell surface and at least one tumor associated antigen selected from the group consisting of GM-2, GD-2, Fetal Antigen and Melanoma Associated Antigen.

Abstract: A glioblastoma-derived angiogenesis inhibiting factor is described. The material is induced in presence of wild type p53, but not by several mutated forms of p53. Various uses of the material are described.

Abstract: Monoclonal receptors raised to immunogenic polypeptides whose amino acid residue sequences correspond to sequences of oncoprotein ligands are disclosed, as are method for the production of those receptors and products and methods that utilize them. The monoclonal receptors bind both to the oncoprotein ligand to a portion of which the polypeptide corresponds in sequence, and to the immunogenic polypeptide to which the receptors were raised.

Abstract: The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

Abstract: Fragments of an endothelial cell proliferation inhibitor and method of use therefor are provided. The endothelial proliferation inhibitor is a protein derived from plasminogen, or more specifically is an angiostatin fragment. The angiostatin fragments generally correspond to kringle structures occurring within the endothelial cell proliferation inhibitor. The endothelial cell inhibiting activity of these fragments provides a means for inhibiting angiogenesis of tumors and for treating angiogenic-mediated disease.

Abstract: The invention describes the RAGE tumor rejection antigen precursor family, including nucleic acids encoding such tumor rejection antigen precursors, tumor rejection antigen peptides or precursors thereof and antibodies relating thereto. Methods and products also are provided for diagnosing and treating conditions characterized by expression of a RAGE tumor rejection antigen precursor.

Abstract: The invention relates to an isolated DNA sequence which codes for an antigen expressed by tumor cells which is recognized by cytotoxic T cells, leading to lysis of the tumor which expresses it. Also described are cells transfected by the DNA sequence, and various therapeutic and diagnostic uses arising out of the properties of the DNA and the antigen for which it codes.

Abstract: A new polyvalent melanoma cell vaccine is disclosed comprised of one or more allogeneic melanoma cell lines which contain effective concentrations of melanoma associated antigens. Further disclosed are a method of stimulating an immunological response by administering the described vaccine as well as a method of prognosticating a patient.

Abstract: Three mammalian are disclosed which are useful in the diagnosis and prognosis of tumors of lymphoid and epithelial origin. The three proteins are immunologically related to each other. The level of expression of the proteins correlates with the malignant potential of lymphoid and epithelial tumors. In addition, in some cases the subcellular location of the proteins is indicative of malignant potential. Antibodies reactive with the proteins are disclosed as diagnostic tools, as are nucleic acid probes and primers for quantitating the messenger RNAs encoding the proteins. Methods for preparing and purifying the proteins are also taught.

Abstract: The breakpoints of the pericentric inversion of chromosome 16 have been cloned. Two genes, one at each breakpoint, have also been identified, as well as several forms of the inversion 16 fusion gene. Diagnostic applications for chromosome 16 abnormalities and, particularly acute myeloid leukemia are also within the scope of the present invention.

Abstract: The present invention relates, in general, to a method of treating inflammation or inhibiting cancer cell metastasis. In particular, the present invention relates to a method of suppressing T cell activation, inhibiting CD44-mediated cell adhesion and CD44-monocyte IL1 release, treating inflammation, and transporting a drug to a site of inflammation.

Abstract: The entire coding region of the gene involved in von Recklinghausen neurofibromatosis (NF1) and a ubiquitously expressed large transcript (NF1LT) of the gene have been identified, cloned and sequenced. With the identification of the NF1 gene and its gene product, nucleic acid probes and antibodies raised to the gene product can be used in a variety of hybridization and immunological assays to screen for NF1 and detect it in its early stages. Conventional and gene therapies can also be developed to treat those afflicted with the disease.

Abstract: Prophylaxis against viral infections, as well as treatment for individuals infected with a virus, can be achieved through the administration of human chorionic gonadotropin (HCG). Exemplary of the viral infections that are amenable to the use of HCG in this regard include those caused by HIV-1, Kaposi's sarcoma herpes virus, molluscipoxvirus and cytomegalovirus. In addition, HCG can be used as a neonatal immune booster via administration to a baby at delivery and, optionally, for the first several months of life, until the infantile immune system matures, in order to prevent HIV transmission and control any low-level viremia, as well as to protect against various other viruses, such as herpes viruses and oncogenic viruses.

Abstract: A new polyvalent melanoma cell vaccine is disclosed comprised of one or more allogeneic melanoma cell lines which contain effective concentrations of melanoma associated antigens. Further disclosed are a method of stimulating an immunological response by administering the described vaccine as well as a method of prognosticating a patient.

Abstract: The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human breast cancer predisposing gene (BRCA2), some mutant alleles of which cause susceptibility to cancer, in particular breast cancer. More specifically, the invention relates to germline mutations in the BRCA2 gene and their use in the diagnosis of predisposition to breast cancer. The present invention further relates to somatic mutations in the BRCA2 gene in human breast cancer and their use in the diagnosis and prognosis of human breast cancer. Additionally, the invention relates to somatic mutations in the BRCA2 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the BRCA2 gene, including gene therapy, protein replacement therapy and protein mimetics.

Abstract: The infusion of TIL586 along with interleukin-2 (IL-2) into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. The present invention relates to the identification of a second tumor antigen recognized by a HLA-A31 restricted CTL clone derived from the TIL586 cell line. This antigen derived from the TRP-2 protein tumor antigen and peptides thereof are capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Modified peptides were also recognized by the CTL clone.

Abstract: Polynucleotide and polypeptide sequences encoding a novel tumor suppressor gene, DPC4, are provided. Also included is a method for detecting a cell proliferative disorder associated with DPC4. DPC4 is a marker which can be used diagnostically, prognostically and therapeutically over the course of disorders associated with DPC4.

Abstract: The invention provides novel uses for n-glycolylated gangliosides, or derivatives and/or oligosaccharides thereof. The invention further provides methods of obtaining such gangliosides, as well as vaccine compositions comprising said gangliosides. The gangliosides may be coupled to carriers and may be accompanied by adjuvants. The vaccine compositions can be used in the treatment of breast cancers, whereby the gangliosides are used to elicit an immune response to corresponding gangliosides on breast tumour cells.

Abstract: A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.

Abstract: This invention relates to the isolation, identification and sequencing of a cancer associated protein, preparation of hybridization probes therefrom, preparation of antibodies thereto, and methods of cancer risk assessment and diagnosis.

Abstract: Three mammalian are disclosed which are useful in the diagnosis and prognosis of tumors of lymphoid and epithelial origin. The three proteins are immunologically related to each other. The level of expression of the proteins correlates with the malignant potential of lymphoid and epithelial tumors. In addition, in some cases the subcellular location of the proteins is indicative of malignant potential. Antibodies reactive with the proteins are disclosed as diagnostic tools, as are nucleic acid probes and primers for quantitating the messenger RNAs encoding the proteins. Methods for preparing and purifying the proteins are also taught.

Abstract: A partial murine cDNA clone, a human cDNA clone, and a partial human genomic clone, each encoding a Box-dependent myc-interacting polypeptide termed Bin1, are provided. Also provided are methods of using the nucleic acid sequences, polypeptides, and antibodies directed against same in the diagnosis and treatment of cancers and hyperplastic disease states.

Abstract: New peptides derived from the MAGE-2 molecule and which bind to HLA-A*0201 molecules are disclosed. Some of these are especially useful because, when complexed to their HLA-A*0201 partner molecules, they induce CTL proliferation.

Abstract: The present invention provides recombinant CEA glycoproteins and methods for their production. These recombinant CEA glycoproteins s lack the C-terminal 26 amino acids which are present in natural CEA and are characterized in that they are free from cross-reactive CEA-like antigens, antigenically indistingiushable from the soluble form of CEA shed from tumor cells, and devoid of the ethanolamine which is present at the C-terminus of natural CEA, and also devoid of the additional amino acids which may be attached to the natural CEA through said ethanolamine. Said recombinant CEA glycoproteins s preferably have the amino acid sequence SEQ ID NO: 1. The CEA glycoproteins s of the invention may be used as reagents in an immunoassay for the diagnosis of neoplastic diseases. The invention also relates to a DNA encoding said recombinant CEA glycoprotein, such as the DNA having the nucleotide sequence SEQ ID NO: 2 or a functional equivalent sequence thereof.

Abstract: An isolated nucleic acid sequence encoding major Yo paraneoplastic antigenic polypeptide is provided by this invention. This invention also provides a purified major Yo antigenic polypeptide and compositions containing the purified major Yo antigenic polypeptide. Further provided by this invention is a monoclonal antibody directed to an epitope on the major Yo paraneoplastic antigenic polypeptide. Compositions containing this monoclonal antibody also are provided by this invention. This invention also provides methods of diagnosis and treatment using the compositions described hereinabove.

Abstract: A method for growing epithelial cells in vitro using soluble proteins secreted by 804G and NBT-II rat bladder carcinoma cells. These proteins stimulate cell attachment and hemidesmosome formation in cells grown in contact with the proteins. The protein is purified from conditioned medium by immunoaffinity chromatography using a monoclonal antibody generated against the protein. The purification of these proteins may be facilitated by culturing the cells under low serum or serum free conditions.

Abstract: Described is a gene situated in the region of the neuroblastoma consensus deletion 1p36.2-p36.1 and which codes for a helix-loop-helix protein with the designation HEIR-1. The gene is affected significantly by allelic tumor deletions in neuroblastomas and correlates inversely both N-myc overexpression in tumors and with N-myc expression in normal development. The cDNA and antibodies coding for HEIR-1 are used for the diagnosis of pathological conditions associated with aberration in the region of the neuroblastoma consensus deletion.

Abstract: A new cell line has been made which is capable of producing an antibody that reacts with melanoma associated tumors cells. Antigens capable of reacting with the new antibody have been isolated and characterized. Methods are disclosed for utilizing the antibody and antigen of the present invention and diagnostic procedures for determining the identity and extent of melanoma associated disease. The compositions of the present invention are disclosed to be useful in other immunological proceedures.

Abstract: A new family of tumor rejection antigen precursors, and the nucleic acid molecules which code for them, are disclosed. These tumor rejection antigen precursors are referred to as GAGE tumor rejection antigen precursors, and the nucleic acid molecules which code for them are referred to as GAGE coding molecules. Various diagnostic and therapeutic uses of the coding sequences and the tumor rejection antigens, and their precursor molecules are described. Tumor rejection antigens are also shown.

Abstract: An isolated nucleic acid sequence encoding Ri paraneoplastic antigenic polypeptide is provided by this invention. This invention also provides a purified Ri antigenic polypeptide and compositions containing the purified Ri antigenic polypeptide. Further provided by this invention is a antibody directed to an epitope on the Ri paraneoplastic antigenic polypeptide. Compositions containing this antibody also are provided by this invention. This invention also provides methods of diagnosis and treatment using the compositions described hereinabove.

Abstract: Tumor rejection antigens derived from tumor rejection precursor MAGE-3 have been identified. These "TRAS" bind to the MHC-class I molecule HLA-A2, and the resulting complexes stimulate the production of cytolytic T cell clones which lyse the presenting cells. The peptides and complexes may be used diagnostically, therapeutically, and as immunogens for the production of antibodies, or as targets for the generation of cytolytic T cell clones.

Abstract: Human HL-60 lectin having an amino acid sequence different from other known animal lectins is disclosed. This is one member of a class of mammalian lectins extractable in lactose or detergent and specific for beta-D-galactosides (14-beta-gal lectin which contains at least one glycosylation site). Recombinant methods and materials for production of the mammalian 14-beta-gal lectins, especially HL-60 lectin, in a variety of hosts, and methods to utilize the resulting lectins are also described. Human HL-60 lectin is found in HL-60 cells and in placental tissue.

Abstract: The invention relates to the identification of complexes of HLA-C-clone 10 and MAGE-1 derived peptides on the surfaces of abnormal cells. The therapeutic and diagnostic ramifications of this observation are the subject of the invention.

Abstract: The invention describes peptides derived from tumor rejection antigen precursor MAGE-2. These peptides bind with HLA-A2 molecules, thus presenting complexes which provoke cytolytic T cell production. The resulting "CTLs" are specific for complexes of HLA-A2 and the peptide. The complexes can be used to generate monoclonal antibodies. The cytolytic T cells produced may be used in the context of immunotherapy, such as adoptive transfer.

Abstract: Tumor rejection antigens derived from tumor rejection precursor MAGE-3 have been identified. These "TRAS" bind to the MHC-class I molecule HLA-A2, and the resulting complexes stimulate the production of cytolytic T cell clones which lyse the presenting cells. The peptides and complexes may be used diagnostically, therapeutically, and as immunogens for the production of antibodies, or as targets for the generation of cytolytic T cell clones.

Abstract: The present invention relates to a gelatinase A inhibitor comprising as an active ingredient a peptide analogue consisting of an active minimum unit of gelatinase A inhibition obtained from APP (.beta.-amyloid precursor) or a peptide analogue comprising it. Gelatinase A can be qualified and quantified using any of the gelatinase A inhibitors according to the present invention.

Abstract: The invention provides methods and compositions for identifying colon cancers in an individual. In one embodiment of the invention, a colon adenocarcinoma-associated protein may be detected in a tissue or body fluid sample of an individual, to provide an indication of the presence of an adenocarcinoma of the colon in the individual. The target adenocarcinoma-associated protein, may be detected, e.g., by reacting the sample with a labeled binding moiety, such as a labeled antibody, capable of specifically binding the protein. In another embodiment, the protein may be detected by isolating one or more colon adenocarcinoma-associated proteins from the sample, separating the proteins by two dimensional gel electrophoresis, and comparing the gel electrophoresis pattern with a standard. The invention provides a wide range of assay methods and compositions which may be used for detecting colon tumors in an individual rapidly and reproducibly, optimally at early stages of the disease.

Abstract: Methods and compositions useful in the detection of human cancer cells and malignant tumors are provided. Certain human autocrine motility factor receptors or proteins (gp78-hAMFR) have been identified which are useful in the detection of human cancer cells and malignant tumors. Methods and assay kits for the detection of human cancer, human cancer cells, and tumors, are provided wherein antibodies or other probes are used which recognize gp78-hAMFR expression. These methods and assay readily distinguish between non-malignant and malignant cancer cells and tumors and can be used to gauge metastatic potential.