The method of treating adenoid cystic carcinoma or other cancer tumors includes the administration of an effective dosage of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling to a patient in need thereof, alone or in combination with other cancer treatment. Non-limiting examples of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling include 4-[(1E)-2-[5,6-Dihydro-5,5-dimethyl-8-(2-phenylethynyl)-2-naphthalenyl]ethenyl]benzoic acid (commonly referred to as “BMS493”) and 4-[2-[5,6-Dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl] ethynyl]benzoic acid (commonly referred to as “AGN193109”). Alternatively, prior to administration of the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling, a direct agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling may be administered to the patient. Non-limiting examples of a direct agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling include all-trans retinoic acid (ATRA), isotretinoin, alitretinoin, and bexarotene.

The present invention is related to a compound of formula (I): a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, a metabolite thereof or a prodrug thereof; for use in a method for the treatment and/or prevention of leukemia, wherein X is selected from the group consisting of N—R.sup.1, O and S; R.sup.1 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl and hydrogen; R.sup.2 is selected from the group consisting of indolyl, substituted indolyl, azaindolyl and substituted azaindolyl; and R.sup.3 is selected from the group consisting of aryl, substituted aryl, unsubstituted heteroaryl, heterocyclyl and substituted heterocyclyl. ##STR00001##

The present invention is related to a compound of formula (I): a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, a metabolite thereof or a prodrug thereof; for use in a method for the treatment and/or prevention of leukemia, wherein X is selected from the group consisting of N—R.sup.1, O and S; R.sup.1 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl and hydrogen; R.sup.2 is selected from the group consisting of indolyl, substituted indolyl, azaindolyl and substituted azaindolyl; and R.sup.3 is selected from the group consisting of aryl, substituted aryl, unsubstituted heteroaryl, heterocyclyl and substituted heterocyclyl. ##STR00001##

The present invention is related to a compound of formula (I): a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, a metabolite thereof or a prodrug thereof; for use in a method for the treatment and/or prevention of leukemia, wherein X is selected from the group consisting of N—R.sup.1, O and S; R.sup.1 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl and hydrogen; R.sup.2 is selected from the group consisting of indolyl, substituted indolyl, azaindolyl and substituted azaindolyl; and R.sup.3 is selected from the group consisting of aryl, substituted aryl, unsubstituted heteroaryl, heterocyclyl and substituted heterocyclyl. ##STR00001##

Provided is a nanosphere for delivery of a therapeutic agent comprising: a polymer matrix; discrete liquid oil droplets dispersed in the polymer matrix; and a therapeutic agent dissolved or dispersed in the oil. In some embodiments, the nanosphere is pegylated. In some embodiments, the nanosphere has a diameter of from about 100 nm to about 300 nm. In further preferred embodiments, the nanosphere has a diameter of from about 150 nm to about 250 nm. In yet further embodiments, the nanosphere has a diameter of from about 180 nm to about 220 nm. In some embodiments, the oil comprises a lipid or a phospholipid. In further embodiments, the lipid or the phospholipid has a melting point below 20° C. In some embodiments, the polymer is a natural, modified or synthetic polymer. In further embodiments, the polymer is biodegradable.

Provided is a nanosphere for delivery of a therapeutic agent comprising: a polymer matrix; discrete liquid oil droplets dispersed in the polymer matrix; and a therapeutic agent dissolved or dispersed in the oil. In some embodiments, the nanosphere is pegylated. In some embodiments, the nanosphere has a diameter of from about 100 nm to about 300 nm. In further preferred embodiments, the nanosphere has a diameter of from about 150 nm to about 250 nm. In yet further embodiments, the nanosphere has a diameter of from about 180 nm to about 220 nm. In some embodiments, the oil comprises a lipid or a phospholipid. In further embodiments, the lipid or the phospholipid has a melting point below 20° C. In some embodiments, the polymer is a natural, modified or synthetic polymer. In further embodiments, the polymer is biodegradable.

Freeze dried active compositions are described. The compositions comprise less than 6.5% by weight water and they may be hydrated or added to end use compositions in order to yield compositions for delivering superior topical benefits to consumers.

Freeze dried active compositions are described. The compositions comprise less than 6.5% by weight water and they may be hydrated or added to end use compositions in order to yield compositions for delivering superior topical benefits to consumers.

This invention relates to systems and methods for evaluating the differentiality of a set of discrete random variables between two or more conditions, such as a malignant condition responding to treatment regime and one that is not. It also provides for the identification and selection of drugs that act in coordinated manner to phenocopy a genetic network of a malignant condition that responds to at least an immune checkpoint blockade agent.

This invention relates to systems and methods for evaluating the differentiality of a set of discrete random variables between two or more conditions, such as a malignant condition responding to treatment regime and one that is not. It also provides for the identification and selection of drugs that act in coordinated manner to phenocopy a genetic network of a malignant condition that responds to at least an immune checkpoint blockade agent.