Abstract: The present invention relates to a combined preparation comprising (i) a modulator of pyruvate kinase M2 (PKM2) activity, and (ii) an agent providing high mobility group box 1 (HMGB1) polypeptide or a derivative thereof. The present invention also relates to the aforesaid combined preparation for use as a medicament and for use in the treatment of inappropriate cellular proliferation, preferably in the treatment of cancer. Moreover, the present invention relates to a method for determining whether a subject suffering from inappropriate cellular proliferation is amenable to a treatment comprising administration of a modulator of PKM2 activity as the only PKM2 inhibitor and to treatment methods related thereto.

Abstract: The present invention relates to a method of determining a metabolic adaptation of a living entity of interest to a first set of environmental conditions and to a second set of environmental conditions comprising (a) determining with a first substrate concentration at least two activities of at least one enzyme comprised in a specimen of said living entity maintained under said first set of environmental conditions and at least two activities of said at least one enzyme comprised in a specimen of said living entity maintained under said second set of environmental conditions, wherein said activities are determined at two non-identical points in time t1 and t2 after starting the determining reaction; (b) determining with a second substrate concentration at least two activities of at least one enzyme comprised in a specimen of said living entity maintained under said first set of environmental conditions and at least two activities of said at least one enzyme comprised in a specimen of said living entity mainta

Abstract: The present invention relates to a high mobility group box 1 (HMGB1) polypeptide, wherein in said HMGB1 polypeptide at least one, preferably two, more preferably three, most preferably all four tyrosine residues at positions corresponding to amino acid positions Y109, Y144, Y155 and/or Y162 of human HMGB1 have been exchanged to an amino acid residue independently selected from glutamic acid, glutamine, aspartic acid, asparagine, homoglutamic acid (2-aminohexanedioic acid), and homoglutamine (2,6-diamino-6-oxohexanoic acid). The present invention further relates to a polynucleotide encoding a polypeptide according to the present invention, to a vector comprising said polynucleotide, and to a host cell comprising said polypeptide, said polynucleotide and/or said vector. Also, the present invention relates to methods, kits, and uses related thereto.

Abstract: The present invention relates to a combined preparation comprising (i) a modulator of pyruvate kinase M2 (PKM2) activity, and (ii) an agent providing high mobility group box 1 (HMGB1) polypeptide or a derivative thereof. The present invention also relates to the aforesaid combined preparation for use as a medicament and for use in the treatment of inappropriate cellular proliferation, preferably in the treatment of cancer. Moreover, the present invention relates to a method for determining whether a subject suffering from inappropriate cellular proliferation is amenable to a treatment comprising administration of a modulator of PKM2 activity as the only PKM2 inhibitor and to treatment methods related thereto.

Abstract: The present invention relates to a high mobility group box 1 (HMGB1) polypeptide, wherein in said HMGB1 polypeptide at least one, preferably two, more preferably three, most preferably all four tyrosine residues at positions corresponding to amino acid positions Y109, Y144, Y155 and/or Y162 of human HMGB1 have been exchanged to an amino acid residue independently selected from glutamic acid, glutamine, aspartic acid, asparagine, homoglutamic acid (2-aminohexanedioic acid), and homoglutamine (2,6-diamino-6-oxohexanoic acid). The present invention further relates to a polynucleotide encoding a polypeptide according to the present invention, to a vector comprising said polynucleotide, and to a host cell comprising said polypeptide, said polynucleotide and/or said vector. Also, the present invention relates to methods, kits, and uses related thereto.

Abstract: A diagnostic method for the prediction of tumor prognosis including the likelihood of formation of metastases or of relapse or local recurrence in tumor related diseases in a mammal and the provision of a therapy recommendation for a patient the enzyme activity of key enzymes of the energy metabolism is determined in fresh tumor tissue or fresh tumor cell mass after 24 hours incubation in a cell culture medium. Incubation reduces nutrition, drug and biopsy/surgery effects on the energy metabolism of the tissue slices or the cell mass. The quotients of enzyme activity of anaerobic enzymes are put in ratio to the enzyme activity of aerobic enzymes or vice versa. Said ratio can be taken into account for prognosis of metastasis and a therapy recommendation.

Abstract: A diagnostic method for the prediction of tumor prognosis including the likelihood of formation of metastases or of relapse or local recurrence in tumor related diseases in a mammal and the provision of a therapy recommendation for a patient the enzyme activity of key enzymes of the energy metabolism is determined in fresh tumor tissue or fresh tumor cell mass after 24 hours incubation in a cell culture medium. Incubation reduces nutrition, drug and biopsy/surgery effects on the energy metabolism of the tissue slices or the cell mass. The quotients of enzyme activity of anaerobic enzymes are put in ratio to the enzyme activity of aerobic enzymes or vice versa. Said ratio can be taken into account for prognosis of metastasis and a therapy recommendation.

Abstract: The current invention relates to a method for treating a subject suffering from cancer comprising administering to said subject a therapeutically effective dose of High Mobility Group B1 (HMGB1) protein or of a polynucleotide comprising a coding region for an HMGB1 gene in an expressible form. Moreover, it relates to the combination of said method with other cancer treatment regimens.