Abstract: The present invention provides a method for efficiently converting methotrexate polyglutamates to methotrexate in a cellular extract by contacting the cellular extract with gamma glutamyl hydrolase under conditions suitable for efficient conversion of methotrexate polyglutamates to methotrexate.

Abstract: The present invention provides methods of diagnosing and monitoring systemic lupus erythematosus by measuring cell-based complement activation products (CB-CAPS) in a subject's blood. In particular, the invention describes a diagnostic method employing the measurement of multiple complement activation products on the surfaces of red blood cells, white blood cells, and platelets (e.g., EC4d, BC4d, PC4d, and ECR1). A diagnostic algorithm utilizing the determined levels of CB-CAPS is also disclosed.

Abstract: The present invention provides methods for determining a level of methotrexate polyglutamates (MTXPGs) in an individual undergoing methotrexate (MTX) therapy and for optimizing dose efficacy of MTX therapy in an individual by genotyping the individual at a polymorphic site in at least one folate pathway gene (e.g., a reduced folate carrier (RFC-1) gene, a gamma glutamyl hydrolase (GGH) gene, etc.). Methods are also provided for determining a level of MTXPGs in an individual undergoing MTX therapy and for optimizing dose efficacy of MTX therapy in an individual by generating a pharmacogenetic index based upon the genotype of the individual at a polymorphic site in an RFC-1 gene and/or a GGH gene.

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 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 for efficiently converting methotrexate polyglutamates to methotrexate in a cellular extract by contacting the cellular extract with gamma glutamyl hydrolase under conditions suitable for efficient conversion of methotrexate polyglutamates to methotrexate.

Abstract: The present invention provides methods for determining a level of methotrexate polyglutamates (MTXPGs) in an individual undergoing methotrexate (MTX) therapy and for optimizing dose efficacy of MTX therapy in an individual by genotyping the individual at a polymorphic site in at least one folate pathway gene (e.g., a reduced folate carrier (RFC-1) gene, a gamma glutamyl hydrolase (GGH) gene, etc.). Methods are also provided for determining a level of MTXPGs in an individual undergoing MTX therapy and for optimizing dose efficacy of MTX therapy in an individual by generating a pharmacogenetic index based upon the genotype of the individual at a polymorphic site in an RFC-1 gene and/or a GGH gene.

Abstract: The present invention provides methods for optimizing clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. The methods of the present invention may further comprise determining the level of at least one long-chain methotrexate polyglutamate (MTXPG) in a sample obtained from the individual. The present invention also provides methods for generating a pharmacogenetic index for predicting clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. In addition, the present invention provides methods for optimizing therapeutic efficacy of chemotherapy in an individual by calculating the level of at least one long-chain MTXPG in a sample obtained from the individual.

Abstract: The present invention provides methods for optimizing clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. The methods of the present invention may further comprise determining the level of at least one long-chain methotrexate polyglutamate (MTXPG) in a sample obtained from the individual. The present invention also provides methods for generating a pharmacogenetic index for predicting clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. In addition, the present invention provides methods for optimizing therapeutic efficacy of chemotherapy in an individual by calculating the level of at least one long-chain MTXPG in a sample obtained from the individual.

Abstract: The present invention provides methods for optimizing clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. The methods of the present invention may further comprise determining the level of at least one long-chain methotrexate polyglutamate (MTXPG) in a sample obtained from the individual. The present invention also provides methods for generating a pharmacogenetic index for predicting clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. In addition, the present invention provides methods for optimizing therapeutic efficacy of chemotherapy in an individual by calculating the level of at least one long-chain MTXPG in a sample obtained from the individual.

Abstract: The present invention provides methods for optimizing clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. The methods of the present invention may further comprise determining the level of at least one long-chain methotrexate polyglutamate (MTXPG) in a sample obtained from the individual. The present invention also provides methods for generating a pharmacogenetic index for predicting clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. In addition, the present invention provides methods for optimizing therapeutic efficacy of chemotherapy in an individual by calculating the level of at least one long-chain MTXPG in a sample obtained from the individual.

Abstract: The present invention provides a method for efficiently converting methotrexate polyglutamates to methotrexate in a cellular extract by contacting the cellular extract with gamma glutamyl hydrolase under conditions suitable for efficient conversion of methotrexate polyglutamates to methotrexate.

Abstract: Described herein are methods of treating a disease by treatment with oral sustained release methotrexate alone or in combination with folates. In some embodiments, these approaches improve the pharmacotherapeutic performance of methotrexate therapy. Described herein are novel pharmaceutical compositions for oral administration. Also described herein are novel pharmaceutical compositions for the controlled, sustained delivery of one or more drugs to the stomach or upper gastrointestinal tract. Further described are novel pharmaceutical compositions with increased gastrointestinal residence time. More particularly, novel pharmaceutical compositions which can simultaneously, float in gastric fluid, adhere to the mucosal surfaces of the gastrointestinal tract, swell to a size which delays passage through the pylorus, are described herein. In some embodiments, the pharmaceutical compositions comprise methotrexate. In some embodiments, the pharmaceutical compositions comprise methotrexate and a folate compound.

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 relates to methods for optimizing therapeutic efficacy or reducing toxicity in a subject receiving a drug providing 6-thioguanine nucleotide. The methods provide determining 6-thioguanine and 6-methyl-mercaptopurine nucleotide concentration levels using an analytical technique having an ionizing source.

Abstract: The present invention provides methods for determining a level of methotrexate polyglutamates (MTXPGs) in an individual undergoing methotrexate (MTX) therapy and for optimizing dose efficacy of MTX therapy in an individual by genotyping the individual at a polymorphic site in at least one folate pathway gene (e.g., a reduced folate carrier (RFC-1) gene, a gamma glutamyl hydrolase (GGH) gene, etc.). Methods are also provided for determining a level of MTXPGs in an individual undergoing MTX therapy and for optimizing dose efficacy of MTX therapy in an individual by generating a pharmacogenetic index based upon the genotype of the individual at a polymorphic site in an RFC-1 gene and/or a GGH gene.

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 methods for optimizing clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. The methods of the present invention may further comprise determining the level of at least one long-chain methotrexate polyglutamate (MTXPG) in a sample obtained from the individual. The present invention also provides methods for generating a pharmacogenetic index for predicting clinical responsiveness to chemotherapy in an individual through genotypic analysis of polymorphisms in at least one gene. In addition, the present invention provides methods for optimizing therapeutic efficacy of chemotherapy in an individual by calculating the level of at least one long-chain MTXPG in a sample obtained from the individual.

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 for efficiently converting methotrexate polyglutamates to methotrexate in a cellular extract by contacting the cellular extract with gamma glutamyl hydrolase under conditions suitable for efficient conversion of methotrexate polyglutamates to methotrexate.