Embodiments of the disclosure encompass methods and compositions related to overcoming or preventing cancer resistance to anti-apoptotic proteins, for example BH3 mimetics. The disclosure provides methods for modulating p73 to reduce cancer resistance to BH3 mimetics including inhibitors of Bcl-2, Bcl-xL, Mcl-1, Bcl-W, A1/BFL-1, or a combination thereof. In specific embodiments, targeting isoforms of p73, such as TAp73 or DNp73, results in reduction of cancer resistance to BH3 mimetics to allow effective treatment of hematological cancers.

This disclosure provides a method of preventing, alleviating or treating a condition (i.e., neutropenia) in a subject in need thereof, the condition characterized by compromised white blood cell production in the subject. The method includes administering to the subject a therapeutically effective amount of a protein complex on the same day as a chemotherapy regimen, wherein the protein complex is a modified human granulocyte-colony stimulating factor (hG-CSF) covalently linked to an immunoglobulin Fc region via a non-peptidyl polymer. The non-peptidyl polymer is site-specifically linked to an N-terminus of the immunoglobulin Fc region, and the modified hG-CSF comprises substitutions in at least one of Cys17 and Pro65.

This disclosure provides a method of preventing, alleviating or treating a condition (i.e., neutropenia) in a subject in need thereof, the condition characterized by compromised white blood cell production in the subject. The method includes administering to the subject a therapeutically effective amount of a protein complex on the same day as a chemotherapy regimen, wherein the protein complex is a modified human granulocyte-colony stimulating factor (hG-CSF) covalently linked to an immunoglobulin Fc region via a non-peptidyl polymer. The non-peptidyl polymer is site-specifically linked to an N-terminus of the immunoglobulin Fc region, and the modified hG-CSF comprises substitutions in at least one of Cys17 and Pro65.

The invention pertains to the use of soluble sodium in the manufacture of a composition or kit of parts for (therapeutically) improving and prolonging blood plasma uridine levels and tissue availability of uridine, and/or for treating or preventing impaired blood plasma uridine levels and tissue availability of uridine, and/or for preventing/treating disorders associated with impaired blood plasma and tissue availability of uridine, in a mammal, preferably a human being, by orally co-administering soluble sodium and uridine in a molar ratio of soluble sodium to uridine of more than 1:1, preferably more than 1.5:1, more preferably more than 2:1, even more preferably at least 2.5:1, even more preferably at least 2.8:1, more preferably 3:1-15:1, most preferably 3:1-10:1, particularly 3:1-5:1.

The invention pertains to the use of soluble sodium in the manufacture of a composition or kit of parts for (therapeutically) improving and prolonging blood plasma uridine levels and tissue availability of uridine, and/or for treating or preventing impaired blood plasma uridine levels and tissue availability of uridine, and/or for preventing/treating disorders associated with impaired blood plasma and tissue availability of uridine, in a mammal, preferably a human being, by orally co-administering soluble sodium and uridine in a molar ratio of soluble sodium to uridine of more than 1:1, preferably more than 1.5:1, more preferably more than 2:1, even more preferably at least 2.5:1, even more preferably at least 2.8:1, more preferably 3:1-15:1, most preferably 3:1-10:1, particularly 3:1-5:1.

The present invention relates to antibodies against human Angiopoietin 2 (anti-ANG-2 antibodies), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

The present disclosure relates to methods for increasing telomere length in one or more human cells and/or increasing genome stability of one or more human cells, for example by contacting one or more human cells with an agent that increases expression of Zscan4 in the one or more human cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a genomic and/or chromosome abnormality, of rejuvenating one or more human cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 are also provided.

The disclosure relates to a pharmaceutical composition comprising any one or combination of PIF peptides or analogs or pharmaceutically acceptable salts thereof. Methods of treating autoimmune disease using the one or a combination of PIF peptide or analogs thereof or pharmaceutically acceptable salts thereof is also disclosed.

The disclosure relates to a pharmaceutical composition comprising any one or combination of PIF peptides or analogs or pharmaceutically acceptable salts thereof. Methods of treating autoimmune disease using the one or a combination of PIF peptide or analogs thereof or pharmaceutically acceptable salts thereof is also disclosed.