Abstract: Cancers, particularly solid tumors (e.g., breast, lung, renal, colon and ovarian cancers and melanomas) and cancers of the hematologic system, e.g., hemopoietic cancers such as leukemias, lymphomas or myelomas, are treated by administration of a therapeutically effective amount of a compound having the formula (1): (I)in which the quinoline ring is substituted by from one to three groups selected from halogen and trifluoromethyl (designated in the formula by “A”), and is optionally further substituted by one or more other moieties and R is (a) NR1R2 in which R1 and R2 are independently hydrogen or C1-C4 alkyl; (b) 2-piperidyl, (c) 2-pyridyl, and (d) 5-(ethyl or vinyl)-quinuclidin-4-yl; an enantiomer of such a compound; a pharmaceutically acceptable salts of such a compound or of an enantiomer thereof; a prodrug of such a compound or of an enantiomer thereof; a metabolite of such a compound or of an enantiomer thereof; and mixtures of two or more of the foregoing.

Abstract: A method for detecting whether methyladenosine phosphatase (MTAse) is present in a cell sample. In one respect, the method comprises adding oligonucleotide probes to the sample, which probes are capable of specifically hybridizing to any MTAse encoding nucleic acid in the sample under conditions favoring that hybridization. Absence of MTAse in a sample is considered to be indicative of malignancy. Polynucleotides encoding MTAse, MTAse peptides and antibodies to MTAse, as well as kits for performing the methods of the invention, are provided.

Abstract: This invention provides methods to identify individuals predisposed to developing osteoarthritis, to diagnose osteoarthritis, and to monitor the progression of the disease. The method also provides methods to identify modulators of bone development that affect a wnt/fzd signaling pathway and methods to prevent or treat osteoarthritis by administering the modulator of bone development.

Abstract: The invention provides derivatives of thiazolo[4,5-d1]pyrimidine and their use as inhibitors of proinflammatory cytokines.

Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.

Abstract: The present invention provides a broad-spectrum, long-lasting, and non-toxic combination of synthetic immunostimulatory agents, which are useful for activating the immune system of a mammal and treating diseases such as cancer and autoimmune disease. These agents include TLR-ligands and ligand analogs which induce interferon production, in combination with inhibitors of inosine monophosphate dehydrogenase (IMPDH), that further enhance the induction of interferon production.

Abstract: The diverse receptor-ligand pairs of the Wnt and frizzled (Fzd) families play important roles during embryonic development, and thus may be overexpressed in cancers that arise from immature cells. The mRNA levels and expression levels of 5 Wnt (Wnt-1, 5a, 7a, 10b, 13) and 2 Fzd (Fzd-2, 5) genes in 10 head and neck squamous carcinoma cell lines (HNSCC) were investigated. In addition, anti-Wnt-1 antibodies were used to study the Wnt/Fzd signalling pathway. These results indicate that HNSCC cell lines overexpress one or more Wnt and Fzd genes, and the growth and survival of a subset of HNSCC may depend on the Wnt/Fzd pathway. Therefore, The Wnt and Fzd receptors may be useful targets for immunotherapy of this common cancer.

Abstract: The present invention provides a method for treating a cancer in a mammal comprising administering an effective amount of an indole compound, in combination with an alkylating agent; to a mammal afflicted with cancer.

Abstract: A method of treating cancer is provided comprising administering an amount of etodolac or analog theteof to a subject afflicted with leukemia that is effective to reduce the viability and/or to sensitize leukemia cells to an anti-cancer agent.

Abstract: A method for delivering a naked or isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of a naked polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.

Abstract: The present invention provides a therapeutic method to treat non-malignant diseases characterized by the excessive tissue growth, e.g., hyperplastic diseases, comprising administering to a mammal (e.g.

Abstract: The present invention provides methods of treating cancer using inhibitors of inosine monophosphate dehydrogenase (IMPDH). The IMPDH inhibitors are combined with compounds that inhibit cellular processes regulated by GTP or ATP. Also provided are prodrugs of the IMPDH inhibitor mizoribine and its aglycone. The prodrugs are useful in practicing the methods of the invention, including immunosuppressive therapy and treatment of cancer by prolonged administration without additional therapeutic compounds.

Abstract: The present invention provides methods of treating cancer using inhibitors of protein kinases. The inhibitors of protein kinases are combined with agents that inhibit a cellular ATP synthetic pathway. Inhibitors of ATP synthesis include inhibitors of de novo purine biosynthesis, inhibitors of the salvage pathway of ATP biosynthesis, and inhibitors of the enzyme inosine monophosphate dehydrogenase.

Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.

Abstract: The present invention provides compounds that act to suppress p53 activity in mammalian cells, and a method to effectively suppress p53 activity in the cells of a mammal subject to a stress or pathology that is ameliorated by such suppression.

Abstract: A gene that encodes an inhibitor of CDK4 has been discovered and its genomic nucleotide sequence has been identified. Susceptibility to certain cancers has been shown to be causatively related to the deletion of, or polymorphisms in, the CDK4I gene. The invention is therefore directed to the gene (CDK4I), the inhibitor protein, as well as therapeutic and diagnostic methods which utilize both the CDK4I gene and the CDK4I protein.

Abstract: A gene that encodes an inhibitor of CDK4 has been discovered and its genomic nucleotide sequence has been identified. Susceptibility to certain cancers has been shown to be causatively related to the deletion of, or polymorphisms in, the CDK4I gene. The invention is therefore directed to the gene (CDK4I), the inhibitor protein, as well as therapeutic and diagnostic methods which utilize both the CDK4I gene and the CDK4I protein.

Abstract: A method for delivering a naked or isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of a naked polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.

Abstract: Immunostimulatory polynucleotide-immunomodulatory molecule conjugate compositions are disclosed. These compositions include a polynucleotide that is linked to an immunomodulatory molecule, which molecule comprises an antigen and may further comprise immunomodulators such as cytokines and adjuvants. The polynucleotide portion of the conjugate includes at least one immunostimulatory oligonucleotide nucleotide sequence (ISS). Methods of modulating an immune response upon administration of the polynucleotide-immunomodulatory conjugate preparation to a vertebrate host are also disclosed.

Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.