The current disclosure provides specific peptides, and derived ionization characteristics of the peptides from the estrogen receptor (ER), progesterone receptor (PR), and/or antigen Ki67 (Ki67) proteins that are particularly advantageous for quantifying the ER, PR, and/or Ki67 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue reagents and protocol, and the ER, PR, and/or Ki67 proteins are quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the ER, PR, and/or Ki67 proteins. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of an ER, PR, and/or Ki67 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenviroment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.

The present invention relates to methods and pharmaceutical compositions for preventing or treating inflammatory bowel diseases.

This invention provides compounds of formula I, pharmaceutical compositions comprising a compound of formula I and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds and intermediates useful in the preparation of same.

Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenviroment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.

Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenvironment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.

A novel omega-3 fatty acid/lipid based nutraceutical composition and a method of optimizing said omega-3 fatty acid/lipid based nutraceutical composition. The nutraceutical composition and method is based on the insight that different forms of high omega-3 fatty acid lipids (e.g. triglyceride form, ethyl ester form, free fatty acid form, phospholipid form) have different molecular modes and levels of action. Specifically the phospholipid form is likely more effective at promoting membrane fluidity and permeability, while the free fatty acid form is likely more effective at regulating cell receptors, such as the PPARa receptors, that are responsible for various metabolic effects including lipid metabolism. The desirability of producing omega-3 compositions that may act synergistically and thus more robustly to improve health and to some extent mimic markers of life extension such as shown by caloric restriction, along with specific optimization methods, markers, and compositions are taught.

Described herein is a bioluminescence resonance energy transfer (BRET) based system and method to monitor ternary complex formation in real-time in live cells with high sensitivity and accuracy. This system transfers energy simultaneously between a luciferase donor and intermediate and terminal acceptors, appropriately chosen to also enable transfer from the intermediate to terminal acceptor while minimizing contaminating signals. The system may also be adapted for quaternary complex detection by including a protein complementation assay (PCA) component. The system is broadly applicable to the detection of any protein ternary/quaternary complex such as those involving nuclear receptors, GPCRs, Receptor Tyrosine Kinase (RTKs), multimeric enzymes or structural proteins.

Fatty acid mimetics are identified as modulators of nuclear receptor TLX (NR2E1) in a subject in need thereof. Methods for treating a disease or condition associated with nuclear receptor TLX (NR2E1) comprise administering a fatty acid mimetic of Formula (I), Formula (II), Formula (III), or a pharmaceutically acceptable salt thereof. Methods for modulating activity of nuclear receptor TLX (NR2E1) or for promoting neurogenesis and/or neural stem cell proliferation include contacting the fatty acid mimetic with nuclear receptor TLX (NR2E1).

The present invention relates to compositions and methods comprising a retinoic acid receptor inhibitor, a retinoic X receptor inhibitor or an inhibitor of an enzyme in the retinoic acid biosynthesis pathway for treatment of a patient having a solid tumor. In some embodiments, the solid tumor is a sarcoma.