Abstract: The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein or aberrant activation of a hedgehog signal transduction pathway, e.g., which involve the use of a steroidal alkaloid or other small molecule.

Abstract: The invention is directed to novel cells that are derived from human embryoid bodies. Such embryoid body-derived (EBD) cells are relatively uncommitted or progenitor (e.g., pluripotent) cells. EBD cells, while not immortal, display long-term proliferation in culture with a normal karyotype and can be cryopreserved and cloned. They can be efficiently transfected with retroviruses and lentivirus and genetically manipulated. Although they have a developmentally broad multilineage expression profile, they do not form tumors when injected into severe combined immunodeficiency (SCID) mice. As a result, EBD cells have a variety of uses, for example, in transplantation therapies.

Abstract: A method of identifying epigenetically silenced genes, e.g., methylation silenced genes, in cancer cells is provided. In addition, methods of identifying a cancer by detecting epigenetic silencing of gene expression are provided, as are methods of treating a subject having such a cancer, for example, a colorectal cancer and/or gastric cancer. Reagents for practicing such methods also are provided.

Abstract: Methods of genomic screening to identify epigenetically silenced genes, including epigenetically silenced tumor suppressor genes are provided. Also provided are methods of detecting a cancer, for example, an esophageal squamous cell carcinoma or a head and neck squamous cell carcinoma, as are methods of treating a subject having such a cancer.

Abstract: Methods are provided for identifying a cell exhibiting unregulated growth associated with methylation-silenced transcription of a suppressor of cytokine signaling (SOCS)/cytokine-inducible SH2 protein (CIS) family member (SOCS/CIS) gene such as the SOCS-1 gene. In addition, methods of treating a cancer patient, wherein cancer cells in the patient exhibit methylation-silenced transcription of SOCS/CIS gene such as a SOCS-1 gene, are provided, as are reagents for practicing such methods.

Abstract: The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G?CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.

Abstract: A human cell line, which lacks major histocompatibility class I (MHC-I) antigens and major histocompatibility class II (MHC-II) antigens and which has been modified to comprise and express (i) a nucleotide sequence encoding an immunomodulator and (ii) a nucleotide sequence encoding a viral antigen, and a method of inducing or stimulating an immune response in a human to a viral-associated disease or cancer comprising administering to the human (i) the aforementioned human cell line in an amount sufficient to induce or stimulate an immune response to the viral associated disease or cancer, (ii) a human cell line, which lacks MHC-I and MHC-11 antigens and which has been modified to comprise and express a nucleotide sequence encoding an immunomodulator, and a human cell line, which lacks MHC-I and MHC-II antigens and which has been modified to comprise and express a nucleotide sequence encoding an antigen of EBV, simultaneously or sequentially in either order, by the same or different routes, in amounts sufficie

Abstract: Chicken growth differentiation factor-8 (GDF-8) is disclosed along with fragments and pharmaceutical compositions thereof.

Abstract: The present invention provides a method for identifying a methylated CpG containing nucleic acid by contacting a nucleic acid with a methylation sensitive restriction endonuclease that cleaves unmethylated CpG sites and contacting the sample with an isoschizomer of the methylation sensitive restriction endonuclease, which cleaves both methylated and unmethylated CpG sites. The method also includes amplification of the CpG-containing nucleic acid using CpG-specific oligonucleotide primers A method is also provided for detecting an age associated disorder by identification of a methylated CpG containing nucleic acid. A method is further provided for evaluation the response of a cell to an agent A kit useful for detection of a CpG containing nucleic acid is also provided. Nucleic acid sequences encoding novel methylated clones.

Abstract: The present invention provides methods relating to chemotherapeutic treatment of a cell proliferative disorder. In particular, a method is provided for predicting the clinical response to certain types of chemotherapeutic agents. Alkylating agents, used for the treatment of certain types of tumors including tumors of the nervous system and lymph system, are efficacious agents when the damage they do to tumor cell DNA is not repaired by cellular DNA repair mechanisms. The present invention provides a method for determining the activity of a gene encoding a DNA repair enzyme, thus providing a prediction of the clinical response to alkylating agents.

Abstract: This invention provides a method for inducing weight loss in an animal by administering to the animal a compound which reduces the expression and/or secretion of neuropeptide Y (NPY). The effect may be accomplished directly, indirectly, or humorally. Preferably, administration of this compound has the effect of increasing malonyl CoA levels in the animal. Compounds administered according to this invention may be inhibitors of fatty acid synthase (FAS), including substituted ?-methylene-?-carboxyl-?-butyrolactones, or inhibitors of malonyl Coenzyme A decarboxylase (MCD). Preferably, the compound is administered in an amount sufficient to reduce the amount and/or duration of expression and/or secretion of NPY to levels at or below those observed for lean animals. In another preferred embodiment, the administration will reduce expression and/or secretion to levels observed for fed or satiated animals; more preferably, administration will reduce the level of NPY below that of fed animals.

Abstract: The present invention relates to the detection of a cell proliferative disorder associated with alterations of microsatellite DNA in a sample. The microsatellite DNA can be contained within any of a variety of samples, such as urine, sputum, bile, stool, cervical tissue, saliva, tears, or cerebral spinal fluid. The invention is a method to detect an allelic imbalance by assaying microsatellite DNA. Allelic imbalance is detected by observing an abnormality in an allele, such as an increase or decrease in microsatellite DNA which is at or corresponds to an allele. An increase can be detected as the appearance of a new allele. In practicing the invention, DNA amplification methods, particularly polymerase chain reactions, are useful for amplifying the DNA. DNA analysis methods can be used to detect such a decrease or increase. The invention is also a method to detect genetic instability of microsatellite DNA.

Abstract: The present invention provides methods and kits for identifying an increased risk of developing cancer in a subject. The methods include analyzing a first biological sample, such as a blood sample, from the subject for loss of imprinting of the IGF2 gene. According to the methods a loss of imprinting is indicative of an increased risk of developing cancer. The method can include analyzing genomic DNA from the sample for altered methylation of the IGF2 gene. The altered methylation for example includes hypomethylation of a differentially methylated region of IGF2, corresponding to SEQ ID NO:1 or a polymorphism thereof. The method can be performed on a subject having no apparent or suspected hyperproliferative disorder such as cancer.

Abstract: We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation.

Abstract: Methods for detection of a cell proliferative disorder, such as cancer, are provided utilizing analysis of target mutant nucleic acids in saliva specimens. The presence of the target mutant nucleic acids is indicative of a neoplastic disorder of the lung or the head and neck.

Abstract: Methods of reducing the risk of transmission of a sexually transmitted pathogen by contacting the pathogen or cells susceptible to infection by the pathogen with a ?-cyclodextrin are provided. Methods for reducing the risk of transmission of a sexually transmitted pathogen to or from a subject by contacting the pathogen or cells susceptible to the pathogen in the subject with a pharmaceutical composition containing a ?-cyclodextrin also are provided. Accordingly, pharmaceutical compositions, which include 1) a ?-cyclodextrin, which is in an amount that blocks passage of the pathogen through lipid rafts in the membrane of a cell susceptible to the pathogen, and 2) a contraceptive, an agent for treating a sexually transmitted disease, a lubricant, or a combination thereof, are provided, as are composition formulated from a solid substrate that contains an amount of ?-cyclodextrin useful for reducing the risk of transmission of a sexually transmitted pathogen.

Abstract: It has been determined that metalloprotease cleavage of a myostatin pro peptide results in activation of a latent inactive myostatin to an active form. Accordingly, methods of identifying agents that modulate metalloprotease mediated activation of myostatin are provided, as are agents identified using such methods. Also provided are methods of modulating muscle growth in an organism by increasing or decreasing metalloprotease mediated cleavage of a myostatin pro peptide.

Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.

Abstract: The present invention provides substantially purified peptide portions of a promyostatin polypeptide. For example, the invention provides proteolytic fragments of a promyostatin polypeptide such as a myostatin prodomain or a mature myostatin peptide, as well as functional peptide portions a myostatin prodomain an myostatin. Also provided is a mutant promyostatin polypeptide, which is resistant to proteolytic cleavage, for example, cleavage into a myostatin prodomain and a mature myostatin peptide. The present invention also provides a polynucleotide encoding a peptide portion of a promyostatin polypeptide. In addition, antibodies that specifically bind a peptide portion of a promyostatin polypeptide are provided. The invention further provides methods of identifying a functional peptide portion of a promyostatin polypeptide.

Abstract: Compositions useful for examining the PKD1 gene are provided. In addition, methods for detecting mutations of the PKD1 gene, which can be associated with autosomal dominant polycystic kidney disease in humans, are provided. Methods for diagnosing a mutant PKD1 gene sequence in a subject also are provided, as are methods of treating a subject having a PKD1-associated disorder.