Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.

The present invention relates to methods and biomarkers for detection and characterization of Langerhans cell histiocytosis in biological samples (e.g., tissue samples, blood samples, plasma samples, cell samples, serum samples). In particular, the present invention provides compositions and methods for diagnosing a patient as having a Langerhans cell histiocytosis by identifying mutations in the MAP2K1 gene or gene products.

The present invention provides isolated epitope peptides derived from TOPK and immunogenic fragments thereof have an ability to induce cytotoxic T lymphocytes (CTLs) and thus are suitable for use in cancer immunotherapy, more particularly as cancer vaccines. The peptides of the present invention encompass both of peptides including a TOPK-derived amino acid sequence and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted and/or added, provided such modified versions have CTL inducibility. Further provided are polynucleotides encoding any of the aforementioned peptides as well as pharmaceutical compositions that include any of the aforementioned peptides or polynucleotides. The peptides, polynucleotides, and pharmaceutical compositions of this invention find particular utility in either or both of the treatment and prevention of a number of cancers.

A method of reducing blood glucose in a subject has been developed. In preferred embodiments, the method involves administering to the subject a specific activator of endogenous mitogen-activated protein kinase kinase 6 (MKK3), mitogen-activated protein kinase kinase 6 (MKK4), mitogen-activated protein kinase kinase 6 (MKK6), p38 mitogen-activated protein kinase (p38MAPK), mitogen-activated kinase-activated protein kinase 2 (MK2), or a combination thereof, in an effective amount to reduce blood glucose in a subject. In other embodiments, the method involves administering to the subject a specific activator to increase X-box binding protein 1 (XBP1) phosphorylation on Thr48 and Ser61 in an effective amount to reduce blood glucose in the subject. Methods of identifying agents for reducing blood glucose in a subject are also provided.

In alternative embodiments, provided are methods for: enhancing drought tolerance of crop plants and trees, enhancing salinity of tolerance of plants such as crop plants, enhancing early monitoring of drought, salinity and cold stress by plants such as crop plants and trees, enhancing stress resistance in plants such as crop plants and trees, by increasing the expression of or the activity of a Raf-like mitogen-activated protein (MAP) kinase kinase (MAPKK) kinase delta B3 family enzyme (or a Raf-like MAPKK kinase delta B3 family enzyme) (a M3K B3 family enzyme) in a plant or a tree cell or a plant or a tree.

Provided herein are recombinant proteins comprising sets of polypeptides that may be used for measurement of protein levels.

Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

The use of mitogen activated kinase inhibition therapy in combination with receptor tyrosine kinase therapy for the treatment of cancer is described.

Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.