Abstract: The present invention relates to chimeric molecules comprising portions of rat PEG-3 (“rPEG-3”) and human GADD34 (“hGADD34”) having apoptotic activity. It is based, at least in part, on the discovery that a chimeric protein comprising amino acids 1-347 of rat PEG-3 fused with residues 418-674 of human GADD34 exhibited anti-proliferative activity when expressed in transformed cells. The present invention provides for this and other rPEG3/hGADD34 chimeras, and the use of such proteins in inhibiting cell proliferation, angiogenesis, and tumor growth.

Abstract: The present invention relates to viral vectors that are targeted to cancer cells. The viral vectors of the invention are adenoviruses having a PEG-3 promoter driving the expression of the viral genes E1A and E1B. The PEG-3 promoter exhibits increased activity in malignant cells. Adenoviruses of the invention show increased replication in malignant cells, thereby producing a cytopathic effect. The viral vectors of the invention further comprise additional genes of interest, and/or may have altered capsid proteins that may enhance infection of and/or target infection to cancer cells. Additional cell types derived from diseased states in which the PEG-3 promoter is selectively active are also therapeutic targets of the viral vectors of the instant invention including those generating allergic, autoimmune and inflammatory responses.

Abstract: The present invention is based, at least in part, on the discovery that Astrocyte Elevated Gene-1 (‘AEG-1’) expression (i) suppresses the Excitatory Amino Acid Transporter-2 (‘EAAT-2’) promoter, thereby inhibiting glutamate transport; (ii) supports anchorage independent colony formation of cells, in which it is synergistic with the RAS oncogene; and (iii) is increased in a number of different malignancies. The invention, in various embodiments, provides for methods of treatment of malignancies and neurodegenerative disorders using inhibitors of AEG-1 activity, and provides for screening assays for identifying other compounds that have therapeutic benefit.

Abstract: The present invention relates to the human Retinoic Acid Inducible Gene-1 (hereafter, “RIG-1”) promoter. The present invention provides for the promoter itself which is inducible by interferon, virus infection, retinoic acid and double-stranded RNA. A further embodiment includes expression constructs comprising the RIG-1 promoter operatively linked to a gene of interest, which may be a reporter gene or a therapeutic gene. It also provides for cells and non-human transgenic animals comprising such expression constructs. In addition, the present invention provides for methods of screening agents for anti-viral activity using RIG-1 promoter activation or inhibition as the basis of the screening system.

Abstract: This invention provides a method for producing a temporally spaced subtracted cDNA library comprising: a) isolating temporally spaced RNAs from cells; b) generating cDNA inserts from the RNAs isolated from step (a); c) producing a temporally spaced cDNA library having clones containing the cDNA inserts generated from step (b); d) producing double stranded cDNA inserts from the temporally spaced cDNA library; e) denaturing the double stranded cDNA inserts; f) contacting the denatured double stranded cDNA inserts produced in step (e) with single-stranded DNAs from another cDNA library under conditions permitting hybridization of the single-stranded DNAs and the double-stranded cDNA inserts; g) separating the hybridized cDNA inserts from the unhybridized inserts; h) generating a cDNA library of the unhybridized inserts, thereby generating a temporally spaced subtracted cDNA library.

Abstract: The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K-ras gene, together with introducing an expressible mda-7 gene, in pancreatic cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.

Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having the melanoma differentiation associated gene (mda-7) or the gene product of the melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier.

Abstract: The invention provides for isolated nucleic acids encoding an Mda-5 polypeptide as shown in SEQ ID NO:1. The invention also provides for isolated nucleic acids comprising derivatives of the sequence of SEQ ID NO:1 that encode polypeptides functionally equivalent to Mda-5. The invention further provides for fragments of the isolated nucleic acid of SEQ ID NO:1 that encode polypeptides having Mda-5 biological activity. Vectors comprising these isolated nucleic acids and host cells comprising these vectors are also provided by the instant invention.

Abstract: The invention provides for an isolated nucleic acid encoding Mda-5 (melanoma differentiation associated gene-5) and an isolated Mda-5 polypeptide. The invention further provides a vector comprising the nucleic acid encoding Mda-5, as well as a host cell comprising the vector. The invention provides an antibody which specifically binds to an Mda-5 polypeptide. The invention further provides a method for determining whether a compound is an inducer of Mda-5 gene expression and assays to determine whether a compound modifies the enzymatic activity of the Mda-5 polypeptide.

Abstract: The present invention provides a method for identifying a gene which is expressed at a modulated level in an aggressive cancer by: (a) measuring baseline expression levels of genes in cancer cells; (b) introducing into the cancer cells an expression vector which directs expression of rat PEG-3; (c) measuring the expression levels of genes in the cells from step (b); and (d) identifying genes, the expression of which is modulated in an aggressive cancer. In another aspect of this invention, the measurement of expression levels of genes in step (a) and/or step (c) comprises measuring mRNA levels. In yet another aspect of the invention, the measurement of expression levels of genes in step (a) and/or step (c) comprises measuring RNA levels. In another aspect of the invention, the genes identified in step (d) are used for diagnosing whether a subject suffers from an aggressive form of cancer.

Abstract: This invention provides for antibodies directed to OLD-35 protein, the product of the OLD-35 gene, which displays enhanced expression during cellular senescence and terminal cell differentiation.

Abstract: This invention provides a method for detecting cancer cells in a sample comprising detection of the expression of a Prostate Tumor Inducing Gene in the sample, wherein a positive detection of the expression indicates the presence of cancer cells in the sample. In an embodiment, the expression is performed by measuring the level of PTI mRNA. The mRNA is measured by reverse transcription-polymerase chain reaction using at least a pair of appropriate primers. It is well known in the art that once the sequence of the Prostate Tumor Inducing Gene is determined, appropriate pair of primers may be selected. This invention also provides the above method, wherein the expression is performed by measuring the level of PTI protein.

Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having the melanoma differentiation associated gene (mda-7) or the gene product of the melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier.

Abstract: The present invention provides for an isolated Mda-7 promoter capable of directing transcription of a heterologous coding sequence positioned downstream therefrom, wherein the promoter is selected from the group consisting of: (a) a promoter comprising the nucleotide sequence shown in SEQ ID NO:1; (b) a promoter comprising a nucleotide sequence functionally equivalent to the nucleotide sequence shown in SEQ ID NO: 1; and (c) a promoter comprising a nucleotide sequence that hybridizes to a sequence complementary to the promoter of (a) or (b) in a Southern hybridization reaction performed under stringent conditions. The invention provides for a host cell comprising the recombinant expression construct as described herein.

Abstract: The present invention relates to methods of inhibiting the proliferation and/or metastasis of a cancer cell by administering, to the cancer cell, a molecule which increases, in the cell or at the cell surface, the amount of a Bivalent Prostate Carcinoma Tumor Antigen-1 (“B-PCTA-1”) protein (referred to as “bivalent” because it comprises both carbohydrate recognition domains (“CRDs”)). It is based, at least in part, on the discovery that increased expression of the full-length open reading frame of the PCTA-1 gene suppressed proliferation of tumor cells in soft agar (a characteristic associated with malignancy and tumor metastasis), whereas increased expression of a PCTA-1 gene lacking the second CRD-encoding region had the opposite effect, increasing the anchorage-independent proliferation of the tumor cells.

Abstract: The present invention provides a vector comprising Protein Translation Peptide Elongation Factor-1 &agr; promoter and nucleic acids encoding reverse tetracycline controlled transactivator, wherein the expression of said transactivator is under the control of Protein Translation Peptide Elongation Factor-1 &agr; promoter.

Abstract: This invention provides a method for preparing a hybridoma cell line which produces an antibody capable of specifically binding to a cell surface-expressed protein which expresses on the surface of one cell type but not the other. This invention also provides a method for preparing a hybridoma cell line which produces an antibody capable of specifically binding to a cell surface-expressed protein. This invention provides a method to prepare a hybridoma cell line which specifically recognizes and binds to a tumor associated antigen associated with a neoplastic, human cell. This invention also provides a method of preparing DNA encoding a cell surface antigen associated with a neoplastic, human cell. This invention further provides an isolated mammalian nucleic acid molecule having the sequence of Prostate Carcinoma Tumor Antigen Gene-1. This invention also provides an isolated mammalian nucleic acid molecule having the sequence of Prostate Tumor Inducing Gene-1.

Abstract: This invention provides a method for detecting cancer cells in a sample comprising detection of the expression of a Prostate Tumor Inducing Gene in the sample, wherein a positive detection of the expression indicates the presence of cancer cells in the sample. In an embodiment, the expression is performed by measuring the level of PTI mRNA. The mRNA is measured by reverse transcription-polymerase chain reaction using at least one pair of approporiate primers. It is well known in the art that once the sequence of the Prostate Tumor Inducing Gene is determined, an appropriate pair of primers may be selected. This invention also provides the above method, wherein the expression is performed by measuring the level of PTI protein.

Abstract: This invention provides an isolated nucleic acid comprising a PEG-3 promoter comprising the nucleotide sequence of −270 to +194 of FIG. 2. The invention also provides a method for identifying an agent that modulates PEG-3 promoter activity using a cell which comprises a PEG-3 promoter operatively linked to a reporter gene, wherein reduced reporter gene expression in the presence of the agent is indicative of an agent that inhibits PEG-3 promoter activity and wherein increased reporter gene expression in the presence of the agent is indicative of an agent that enhances PEG-3 promoter activity. The invention provides a method for treating cancer in a subject which comprises administering a nucleic acid comprising a PEG-3 promoter operatively linked to a gene-of-interest, wherein the gene-of-interest is selectively expressed in cancerous cells in the subject and such expression results in growth suppression or death of the cancerous cells.

Abstract: The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K-ras gene, together with introducing an expressible mda-7 gene, in pancreatic cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.