Abstract: The present invention relates to methods and compositions for treating cancers by reducing the expression or activity of one or more of the genes encoding protein kinases ATR, MAST2, MAP3K6, TBK1, ADRBK2, CDKL2, LATS2, STK32B, STK11, DDR13 PSKH2, and NEK8, and/or the encoded kinases. The invention also relates to methods and compositions for determining the responsiveness of a cancer patient to anti-cancer drugs based on the status of one or more of such kinases. The invention further relates to methods and compositions for screening compounds that can be used to modulate the expression/activity of these kinases.

Abstract: Provided herein are isolated nucleic acid molecule corresponding to miR145 that are useful in treating colon cancer. The disclosed miR145 nucleic acids specifically bind the 3? UTR within endogenous IRS-I such as to suppress or inhibit colon cell proliferation.

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract: The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

Abstract: The invention provides methods and compositions for gene silencing by RNA interference. In particular, the invention provides methods for gene silencing or RNA knockdown using small interfering RNAs (siRNAs) having partial sequence homology to its target gene. The invention also provides methods for identifying common and/or differential responses to a plurality of different siRNAs targeting a gene. The invention also provides methods for evaluating the relative activity of the two strands of an siRNA. The invention further provides methods of designing siRNAs for gene silencing. The invention further provides methods of using siRNAs as therapeutics for treatment of diseases.

Abstract: In a first aspect, the invention provides methods for screening for modulators of a target protein, comprising the steps of contacting a target protein with a candidate agent and determining whether the candidate agent modulates the activity of the target protein, wherein the target protein comprises a sequence that has more than 80% amino acid sequence identity to KIF14 (SEQ ID NO:2) or the KIF14 motor domain (SEQ ID NO:3). In a second aspect, the invention provides methods for modulating cell proliferation comprising administering to a cell an effective amount of a modulator of the activity of a target protein. Some embodiments of this aspect provide methods for treating a subject with a cellular hyperproliferation disorder, such as cancer. In a third aspect, the invention provides methods for identifying candidate subjects for treatment with an inhibitor of the activity of a target protein.

Abstract: Methods for identifying modulators of PPIL2 are described. The methods are particularly useful for identifying analytes that antagonize PPIL2's effect on processing of amyloid precursor protein to A? peptide and thus useful for identifying analytes that can be used for treating Alzheimer disease.

Abstract: The present invention relates to genetic markers whose expression is correlated with progression of CML. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate chronic phase individuals from those in blast crisis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.

Abstract: Methods and compositions are provided that are useful for detecting and reporting a plurality of different target polynucleotide sequences in a sample, such as polynucleotides corresponding to a plurality of different genes expressed by a cell or cells. In particular, the invention provides methods for screening a plurality of candidate polynucleotide probes to evaluate both the sensitivity and the specificity with which each candidate probe hybridizes to a target polynucleoide sequence. Candidate polynucleotide probes can then be ranked according to both their sensitivity and specificity, and probes that have optimal sensitivity and specificity for a target polynucleotide sequence can be selected. In one embodiment, polynucleotide probes can be selected according to the methods described herein to prepare “screening chips” wherein a large number of target polynucleotide sequences are detected using a single microarray have a few (e.g., 1-5) probes for each target polynucleotide sequence.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: The present invention provides a method for inhibiting an immune reponse and a method for inhibiting rejection of transplanted tissues. This method comprises preventing an endogenous molecule on a cell selected from the group consisting of gp39 and CD40 antigens from binding its endogenous ligand and preventing an endogenous molecule on a cell selected from the group consisting of CTLA4, CD28, and B7 antigens from binding its endogenous ligand. The prevention of such molecules from binding their ligand thereby blocks two independent signal pathways and inhibits the immune response resulting in transplanted tissue rejection.

Abstract: The invention provides a method for identifying one or more genes in a cell of a cell type which interact with, e.g., modulate the effect of, an agent, e.g., a drug. For example, an identified gene may confer resistance or sensitivity to a drug, i.e., reduces or enhances the effect of the drug. The invention also provides STK6 and TPX2 as a gene that exhibits synthetic lethal interactions with KSP encoding a kinesin-like motor protein, and methods and compositions for treatment of diseases, e.g., cancers, by modulating the expression of STK6 or TPX2 gene and/or the activity of STK6 or TPX2 gene product. The invention also provides genes involved in cellular response to DNA damage, and their therapeutic uses.

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract: Thermally stable cytosine deaminase (CDase), and the gene coding therefor, is disclosed as well as methods of isolating, purifying, and recombinantly producing the same. The thermally stable CDase can be isolated from Saccharomyces cerevisiae. The yeast isolated enzyme has a molecular weight of approximately 32 kDa, as determined by gel filtration chromatography, and is composed of two subunits, each with a molecular weight of about 17 kDa. Thermally stable yeast CDase so purified shows no significant sequence homology with other known sequenced proteins.

Abstract: Thermally stable cytosine deaminase (CDase), and the gene coding therefor, is disclosed as well as methods of isolating, purifying, and recombinantly producing the same. The thermally stable CDase can be isolated from Saccharomyces cerevisiae. The yeast isolated enzyme has a molecular weight of approximately 32 kDa, as determined by gel filtration chromatography, and is composed of two subunits, each with a molecular weight of about 17 kDa. Thermally stable yeast CDase so purified shows no significant sequence homology with other known sequenced proteins.

Abstract: The present invention is concerned with novel monoclonal antibodies which define a glycolipid antigen associated with human non-small cell lung carcinomas ("NSCLC") and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in lung tissue and other human tissue. The method involves examining the human tissue for the presence of a glycolipid antigen having the characteristics of a ganglio-N-triosylceramide.

Abstract: The present invention is concerned with novel monoclonal antibodies which define a gylcolipid antigen associated with human non-small cell lung carcinomas ("NSCLC") and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagonostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in lung tissue and other human tissue. The method involves examining the human tissue for the presence of a glycolipid antigen having the characteristics of a ganglio-N-triosylceramide.

Abstract: The present invention is concerned with novel monoclonal antibodies which define a glycolipid antigen associated with human non-small cell lung carcinomas ("NSCLC") and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. Also disclosed in a novel glycolipid antigen. The invention also comprises a method for determining the presence of a malignant condition in lung tissue and other human tissue. The method involves examining the human tissue for the presence of a glycolipid antigen having the terminal carbohydrate sequence: GalNAc.beta.l.fwdarw.4Gal.beta.l.fwdarw.3GalNAc.beta.l.fwdarw.4Gal.beta.l. fwdarw.R.

Abstract: The present invention is concerned with two novel monoclonal antibodies which define carbohydrate antigens associated with human non-small cell lung carcinomas ("NSCLC") and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in the lung of a subject. The method involves examining tissue from the subject for the presence of antigens which are Le.sup.x or Le.sup.y antigen or which have the characteristics of Le.sup.y and Le.sup.x.

Abstract: The present invention is concerned with novel monoclonal antibodies which define antigens associated with human non-small cell lung carcinomas ("NSCLC"). The antibodies bind to normal human cells to a lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods.