Abstract: This invention provides for nucleotide sequences that encode CAIR proteins correlated with cellular resistance to carboxyamido-triazole (CAI) and functionally equivalent compounds. The invention further provides for methods of detecting CAI resistance in biological samples and for cell lines that grow and proliferate in the presence of CAI and functionally equivalent compounds.

Abstract: A light generating dry disposable device for determining the presence of analytes in a test sample is disclosed. The device comprises a first zone containing conjugated ligand which is capable of reacting with analytes in the test sample. The ligand is conjugated with a photoprotein or related enzyme. The device further comprises a second trapping zone comprising immobilized analyte. The device also includes a third zone containing a reporter system that activates light generation by the conjugate. The conjugates are maintained in the first zone such that they are removable from the first zone when reacted with the soluble analytes from the test sample passing through the first zone, but not removed from the second trapping zone in the absence of such analytes. The third zone contains material capable of reacting with the photoprotein- or enzyme-linked ligand to produce a light-emitting reaction which indicates the presence of the analyte being tested. The present invention provides dry flow through zones.

Abstract: A discovery underlying this invention is the concordance between particular cellular signaling mechanisms and cancer cell growth and metastasis. It has now been discovered that certain compounds inhibit the signal transduction required for the maintenance and driving of the malignant process. These compounds are also effective for the in vivo treatment of solid tumors and related disease states. This invention provides a method for the use of these compounds to inhibit the invasion and metastasis of malignant solid tumors in mammals. This invention further provides a method for using related compounds to treat diseases involving aberrant signal transduction pathways. Some of the compounds used in the methods of the present invention are novel and constitute another aspect of this invention.

Abstract: The present invention relates to the development of a modified substrate capture immunoassay useful in the detection of a neutral metalloproteinase enzyme, type IV collagenase. Capture and immobilization of this enzyme can be achieved by coating the microtiter plate with gelatin, an alternative substrate for this enzyme. The captured enzyme can then be detected by affinity purified rabbit anti-type IV collagenase antibodies prepared against synthetic peptides from the amino terminus of the enzyme. Soluble type IV collagenase can readily be detected in samples known to contain this enzyme. Using purified enzyme this assay method can detect less than 50 ng of latent type IV collagenase. Using EDTA, an inhibitor of this metalloproteinase, gelatin binding can be shown to be independent of catalytic activity.

Abstract: A method of direct extraction of cellular material from a tissue sample which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extracted zone(s) of cells is subjected to analysis. The overall process of identifying, extracting, transporting, and analyzing the extracted zones(s) of cells can be fully automated.

Abstract: A method of microdissection which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes an activatable adhesive layer which provides chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated the transfer surface and tissue sample are separated. During separation the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample.

Abstract: The invention provides a method of increasing the sensitivity of a cell to a DNA damaging agent comprising increasing the amount of an NM23 in the cell. The method is especially useful for increasing the sensitivity of tumor cells to chemotherapy and radiation.

Abstract: The present invention relates, in general, to a method for diagnosing cancer susceptibility based on alterations in the nm23 gene. In particular, the present invention relates to a method of identifying individuals at risk for developing a primary cancer or at risk for suffering treatment failure, morbidity, or mortality associated with cancer. The invention further relates to a means of using genetic methods to predict individuals at increased risk for developing distant metastases.

Abstract: Angiogenesis is a composite of regulated proliferation and regulated invasion occuring in a variety of normal and pathologic conditions. Compound 1 and related analogs are useful for inhibiting angiogenesis in a host and offer a novel approach to the treatment of cancer, diabetic retinopathy, hemangiomata, vasculidities and other diseases associated with angiogenesis.

Abstract: The present invention relates, in general, to autotaxin. In particular, the present invention relates to a DNA segment encoding autotaxin; recombinant DNA molecules containing the DNA segment; cells containing the recombinant DNA molecule; a method of producing autotaxin; antibodies to autotaxin; and identification of functional domains in autotaxin.

Abstract: A method of inhibiting the invasion and metastasis of malignant solid tumors in mammals, said method comprising administering to said mammal an anti-proliferative, anti-invasive and anti-metastasis effective amount of a compound selected from the group of formulas consisting of: ##STR1## wherein: p is an integer of from 0 to 4;Ar.sup.1 is a moiety selected from the group consisting of --Ar.sup.2 --X--Ar.sup.3, phenyl, trioxaadamantyl, anthracenyl, anthraquinonyl, naphthyl, phenanthryl, and substituted versions thereof;Ar.sup.2 and Ar.sup.3 are each aromatic moieties independently selected from the group consisting of phenyl, naphthyl, and substituted versions thereof;X is a linking moiety selected from the group consisting of O, S, SO.sub.

Abstract: Inappropriate degradation of extracellular matrix molecules by metalloproteinases plays an important role in a wide variety of pathologic conditions including neoplasia and arthritis. The present invention is an isolated protein of approximately 23,000 daltons in size which binds to metalloproteinases with high affinity, can be purified using affinity chromatography on solid phase metalloproteinases, and is potentially useful for therapy of pathologic conditions involving the inappropriate production of metalloproteinases. This protein is characterized by the presence of the following amino acid sequences:CSCSPVHPQQAFCNADVVIRAKAVSEKEVDSGNPIYGNNIKDIEFIYTAPSEAVCGVELDVEGKKRHITLCDFIVPWDTLSTTQKKSLNHRYQQGCEECKITRCPMIPCYISSPDECLWTDTVVKFFACIKRHITLCDFIVPWSQIADXLSSWith the positions of the cysteine residues and associated disulfide bridges required for biologic activity.

Abstract: This invention provides for nucleotide sequences that encode CAIR proteins correlated with cellular resistance to carboxyamido-triazole (CAI) and functionally equivalent compounds. The invention further provides for methods of detecting CAI resistance in biological samples and for cell lines that grow and proliferate in the presence of CAI and functionally equivalent compounds.

Abstract: A new method of detecting cancer by determining the presence of autocrine motility factor (AMF) in the body fluid is described. The method utilizes induction of motility in suitable responder cells by a sample of the body fluid. If the responder cells demonstrate motility, cancer is indicated in the person from whom the body fluid was obtained.

Abstract: Calcium homeostasis is an important regulator of MMP-2 transcription, activation and activity. Disclosed herein are compounds which inhibit the expression of matrix metalloproteinases in cells. Pharmaceutical application of these compounds to inhibit the expression of MMPs offers a new approach to cancer treatment as well as treatment for nerve healing, degenerative cartilagenous diseases, decubitus ulcers, arthritis, Alzheimer's disease, wound healing, proliferative retinopathy, proliferative renal diseases, corneal ulcers and fertility problems.

Abstract: The present invention is an isolated protein of 21,600 Da which binds to both latent and activated type IV collagenase with high affinity at 1:1 molar stoichiometry, thereby abolishing enzyme activity. The protein is purified by affinity chromatography on solid phase metalloproteinase, or solid phase metalloproteinase substrates which bind the enzyme-inhibitor complex. The complete primary structure of this protein (initially called CSC-21K), as determined by sequencing overlapping peptides spanning the entire protein, reveals homology with a protein called TIMP, Tissue Inhibitor of Metalloproteinases. In addition, a cDNA for this novel inhibitor, now designated TIMP-2, was cloned from a melanoma cell and its sequence was compared with that of human TIMP-1. Northern blots of melanoma cell mRNA showed two distinct transcripts of 0.9 kb and 3.5 kb which are down-regulated by transforming growth factor-.beta., and are unchanged by phorbol ester treatment.

Abstract: A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity.

Abstract: The present invention provides compositions and methods for the treatment of cancer in a subject wherein compounds of formula I defined herein in combination with paclitaxel or other modified taxane analogs provide enhanced anticancer effects over the effects achieved with the individual compounds.

Abstract: A compound having the formula: ##STR1## and pharmaceutically acceptable salts thereof.

Abstract: A discovery underlying this invention is the concordance between particular cellular signaling mechanisms and cancer cell growth and metastasis. It has now been discovered that certain compounds inhibit the signal transduction required for the maintenance and driving of the malignant process. These compounds are also effective for the in vivo treatment of solid tumors and related disease states. This invention provides a method for the use of these compounds to inhibit the invasion and metastasis of malignant solid tumors in mammals. This invention further provides a method for using related compounds to treat diseases involving aberrant signal transduction pathways. Some of the compounds used in the methods of the present invention are novel and constitute another aspect of this invention.