Abstract: The present invention provides novel recombinant baculovirus expression systems for expressing foreign genetic material in a host cell. Such expression systems are readily adapted to an automated method for expression foreign genetic material in a high throughput manner. In other aspects, the present invention features a novel automated method for determining the function of foreign genetic material by transfecting the same into a host by way of the recombinant baculovirus expression systems according to the present invention.

Abstract: Methods and compositions for treating cancer consisting of viral DNA in association with liposomal material, the viral DNA substantially incapable of encoding a functional viral oncoprotein capable of binding to a functional tumor suppressor gene product in a neoplastic cell, and the viral DNA capable of replicating and forming infectious virus in neoplastic cells thereby killing the neoplastic cells and substantially incapable of replicating and forming infectious virus in non-neoplastic cells that have the tumor suppressor protein.

Abstract: Identification, characterization and expression of nucleotides that encode phosphatidylinositol-3' kinase associated protein(s) that bind to the intermediate SH2 domain on the regulatory subunit of PI3K, p85, by the associated protein(s) C-terminal amino acids, and that exhibit a bromodomain are described, as well as methods of using such proteins for medical applications, including diagnosis and treatment cell growth disorders.

Abstract: Methods and compositions for treating neoplastic conditions by viral-based therapy are provided. Mutant virus lacking viral proteins which bind and/or inactivate p53 or RB are administered to a patient having a neoplasm which comprises cells lacking p53 and/or RB function. The mutant virus is able to substantially produce a replication phenotype in neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 and/or RB function. The preferential generation of replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.

Abstract: A novel human serine protein kinase, human p21-protein activated serine kinase p65 protein, referred to as hPAK65, and methods for its preparation and use are provided. Nucleic acids encoding hPAK65 and methods for their use in preparing hPAK65 as well as in preparing and identifying hPAK65 analogs are provided. Methods provided for the use of hPAK65 protein and its protein fragments, such as those that retain at least one hPAK65 activity, that include screening libraries of agents for candidates that modulate hPAK65 activity. Methods are provided to identify agents that modulate the interaction of hPAK65 with rho-like p21 GTPases, particularly rac1 and CDC42Hs binding to hPAK65 and subsequent activation of hPAK65 serine protein kinase activity, that modulate hPAK65 serine protein kinase activity, and that modulate hPAK65 effect on p21 protein GTPase activity.

Abstract: Provided are novel phospholipase D DNA and amino acid sequences. The sequences are useful in methods and compositions for identifying phospholipase D mediator molecules which are in turn useful in therapeutic pharmacuetical compositions for treating rheumatoid arthritis, psoriasis, ulcerative colitis, in wound healing and for treating other diseases or conditions characterized by exhibition of an inflammatory response or in the treatment of cancer and other diseases characterized by pathogenic mitogenicity.

Abstract: Methods and compositions for treating neoplastic conditions by viral-based therapy are provided. Mutant virus lacking viral proteins which bind and/or inactivate p53 or RB are administered to a patient having a neoplasm which comprises cells lacking p53 and/or RB function. The mutant virus is able to substantially produce a replication phenotype in neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 and/or RB function. The preferential generation of replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.

Abstract: Compositions of matter consisting of a family of related nucleotide sequences that encode proteins, termed BRCA1 Modulator Proteins, that bind to the tumor suppressor gene product BRCA1, and methods of using the nucleotide sequences and the proteins encoded thereby, to diagnose and/or treat disease where the BRCA1 Modulator Proteins have an apparent molecular weight of 45-97 kdaltons and are characterized by having at least one leucine zipper domain, and optionally a zinc finger domain.

Abstract: Methods and compositions for determining the tumor suppressor status of cells are described, preferably as pertaining to the p53 status of tumor cells, and preferably in vivo using a recombinant construct consisting of a first polynucleotide sequence that encodes a reporter molecule and a second p53 binding polynucleotide sequence that is operably linked to the first polynucleotide sequence such that binding of p53 to the second polynucleotide sequence causes the expression of the reporter molecule which can be detected or quantified.

Abstract: Methods and compositions for treating neoplastic conditions by viral-based therapy are provided. Mutant virus lacking viral proteins which bind and/or inactivate p53 or RB are administered to a patient having a neoplasm which comprises cells lacking p53 and/or RB function. The mutant virus is able to substantially produce a replication phenotype in neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 and/or RB function. The preferential generation of replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.

Abstract: The present invention relates to the discovery, identification and characterization of nucleotides that encode the G protein regulated phosphatidylinositol-3'kinase, a heterodimeric enzyme which produces the intracellular messenger phosphatidylinositol (3,4,5)-triphosphate in response to activation of trimeric G protein-linked receptors. This novel protein, comprised of a catalytic subunit, p120, and a regulatory subunit, p101, is found in cells of hematopoietic origin and is involved in immune system responses which cause inflammation. The presence of p101 subunit is largely responsible for the dramatic stimulation of kinase activity in the presence of activated trimeric G proteins.

Abstract: The invention provides compositions and methods for screening for agents which are modulators of bcl-2 function and can modulate bcl-2-mediated apoptosis and/or modulate neoplastic and immune conditions dependent upon bcl-2 function. The invention also provides a composition comprising a substantially pure protein complex comprising a R-ras polypeptide and a bcl-2 polypeptide.

Abstract: Methods and compositions for treating neoplastic conditions by viral-based therapy are provided. Mutant virus lacking viral proteins which bind and/or inactivate p53 or RB are administered to a patient having a neoplasm which comprises cells lacking p53 and/or RB function. The mutant virus is able to substantially produce a replication phenotype in neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 and/or RB function. The preferential generation of replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.

Abstract: The invention provides compositions and methods for screening for agents which are modulators of bcl-2 function and can modulate bcl-2-mediated apoptosis and/or modulate neoplastic and immune conditions dependent upon bcl-2 function. The invention also provides a composition comprising a substantially pure protein complex comprising a R-ras polypeptide and a bcl-2 polypeptide.

Abstract: The reverse two-hybrid method has been designed to provide a practical and efficient means of utilizing yeast cell-based assays to screen for molecules that can inhibit protein-protein interactions of interest. Existing two-hybrid systems involve reconstitution in yeast of a transcriptional activator that drives expression of a "reporter" gene such as HIS3 or lacZ. Attempts to utilize these existing systems for drug discovery would necessarily involve screening for molecules that interfere with the transcriptional read-out, and would be subject to detecting any compound that non-specifically interfered with transcription. In addition, since currently used reporter genes encode long-lived proteins, the assay would have to be performed over a lengthy time period to allow for decay of the preexisting reporter proteins. Any compound that would be toxic to yeast over this time period would also score as a "hit".

Abstract: A method of isolating and purifying toxin conjugates using hydrophobic interaction chromatography. Crude conjugate mixtures are sized to remove unconjugated toxin, and loaded onto a column filled with a suitable hydrophobic gel. Elution is effected with salt solutions of decreasing ionic strength, which salt solutions optionally include increasing amounts of an organic solvent. Toxin conjugate substantially free of unconjugated Ig and unconjugated toxin is provided.