Abstract: The present invention provides compositions and methods for detecting the activation states of components of signal transduction pathways in tumor cells. Information on the activation states of components of signal transduction pathways derived from use of the invention can be used for cancer diagnosis, prognosis, and in the design of cancer treatments.

Abstract: The present invention provides a compliance system that contains at least one dispenser including at least one individual dose of an anti-folate therapeutic and at least one individual dose of a folic acid analog, each individual dose of anti-folate therapeutic and folic acid analog positioned in one or more individual compartments. Such a dispenser can have, for example, suitable indicia marked in association with each individual compartment, thereby identifying each compartment with the day or time when the enclosed anti-folate therapeutic or folic acid analog should be administered.

Abstract: The present invention provides methods for analyzing genetic and/or metabolite biomarkers to individualize methotrexate (MTX) therapy. For example, the assay methods of the present invention are useful for predicting whether a patient will respond to MTX and/or has a risk of developing toxicity to MTX based upon the genotype of one or more folate pathway genes. The assay methods of the present invention are also useful for optimizing the dose of MTX in a patient already receiving the drug to achieve therapeutic efficacy and/or reduce toxic side-effects based upon the genotype of one or more folate pathway genes. In addition, the assay methods of the present invention are useful for predicting or optimizing the therapeutic response to MTX in a patient based upon the methotrexate polyglutamate and/or folate polyglutamate levels in a sample from the patient.

Abstract: The present invention provides a method of determining thiopurine methyltransferase (TPMT) activity in a subject. The method includes the steps of reacting sample obtained from the subject with a thiopurine derivative that is not 6-mercaptopurine to produce a methylated purine product; contacting the reacted sample with acid, thereby precipitating proteinaceous material from the reacted sample; separating supernatant from the precipitated proteinaceous material; and detecting in the supernatant the methylated purine product, where the amount of the methylated purine product indicates a level of thiopurine methyltransferase activity in the subject. In a method of the invention, the subject can be, for example, an inflammatory bowel disease patient. In one embodiment, the acid used to precipitate proteinaceous material is perchloric acid, for example, 70% perchloric acid. In another embodiment, the thiopurine derivative used as a substrate is 6-thioguanine.

Abstract: The present invention provides a method of diagnosing the presence or severity of liver fibrosis in an individual by detecting ?2-macroglobulin (?2-MG) in a sample from the individual; detecting hyaluronic acid (HA) in a sample from the individual; detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from the individual; and diagnosing the presence or severity of liver fibrosis in the individual based on the presence or level of ?2-MG, HA and TIMP-1.

Abstract: The present invention provides methods for diagnosing the presence or severity of inflammatory bowel disease (IBD) in an individual and methods for stratifying IBD by determining the level of one or more IBD markers in a sample from the individual and calculating an index value using an algorithm based upon the level of the IBD markers. Methods for monitoring the efficacy of IBD therapy, monitoring the progression or regression of IBD, and optimizing therapy in an individual having IBD are also provided.

Abstract: The present invention provides a method for determining a level of a methotrexate polyglutamate (MTXPG) in a cellular extract by resolving at least one MTXPG in a cellular extract obtained from a human undergoing methotrexate therapy; and detecting at least one resolved MTXPG, thereby determining a level of the resolved MTXPG. A method of the invention can be useful, for example, for determining a level of MTXPG3, MTXPG4 or MTXPG5 or for determining a level of each methotrexate polyglutamate species (MTXPG1 to MTXPG7) present in the cellular extract.

Abstract: The present invention provides a method of determining thiopurine methyltransferase (TPMT) activity in a subject. The method includes the steps of reacting sample obtained from the subject with a thiopurine derivative that is not 6-mercaptopurine to produce a methylated purine product; contacting the reacted sample with acid, thereby precipitating proteinaceous material from the reacted sample; separating supernatant from the precipitated proteinaceous material; and detecting in the supernatant the methylated purine product, where the amount of the methylated purine product indicates a level of thiopurine methyltransferase activity in the subject. In a method of the invention, the subject can be, for example, an inflammatory bowel disease patient. In one embodiment, the acid used to precipitate proteinaceous material is perchloric acid, for example, 70% perchloric acid. In another embodiment, the thiopurine derivative used as a substrate is 6-thioguanine.

Abstract: The present invention provides a highly sensitive method of diagnosing inflammatory bowel disease (IBD) in an individual. The method includes the steps of isolating a sample from the individual; determining by non-histological means whether the sample is positive for anti-neutrophil cytoplasmic antibodies (ANCA); determining whether the sample is positive for anti-Saccharomyces cerevisiae immunoglobulin A (ASCA-IgA); determining whether the sample is positive for anti-Saccharomyces cerevisiae immunoglobulin G (ASCA-IgG); and diagnosing the individual as having IBD when the sample is positive for ANCA, ASCA-IgA or ASCA-IgG, and diagnosing the individual as not having IBD when the sample is negative for ANCA, ASCA-IgA and ASCA-IgG, provided that the method does not include histological analysis of neutrophils.

Abstract: The present invention provides methods based on serological and genetic markers for diagnosing clinical subtypes of Crohn's disease (CD) having characteristic responsiveness to anti-Th1 cytokine therapy. In the methods of the inventions the presence of perinuclear anti-neutrophil antibody (pANCA), the presence of the TNFa10b4c1d3e3 haplotype or the presence TNFa11b4c1d3e3 haplotype each are independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. In addition, the presence of the homozygous TNF-&bgr; 1111 haplotype involving the TNFc, aa13L, aa26 and NcoI loci is independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. The presence of speckling anti-pan polymorphonuclear antibody (SAPPA) is diagnostic of a clinical subtype of CD having a superior clinical response to anti-Th1 cytokine therapy.