Abstract: Some embodiments of the methods and compositions provided herein include methods of reducing surgery-induced metastases in a subject with cancer following surgery to remove at least one solid tumor, comprising an NADPH oxidase inhibitor to said subject.

Abstract: The present invention provides methods of treating cancer in a subject, preventing or delaying relapse to a cancer in a subject in remission, prolonging remission from cancer, increasing survival, and decreasing or alleviating cancer symptoms comprising a) administering histamine dihydrochloride and an inhibitor of the Programmed cell Death protein 1 (PD-1)/Programmed Death Ligand 1 (PD-L1) or b) administering an agent that decreases reactive oxygen species (ROS) optionally, together with a histamine receptor agonist. The present invention also provides methods of predicting the efficacy of a cancer treatment based on a re-distribution of cytotoxic T cells, frequency of NK cells, or other biochemical changes, and related methods of preventing relapse to cancer and for prolonging remission from a cancer. Related kits and compositions are also provided.

Abstract: Some embodiments provided herein relate to methods and compositions for reducing the risk of relapse of a hyperproliferative disorder, such as acute myeloid leukemia (AML), in a subject in which the hyperproliferative cells of the subject exhibit a normal karyotype and/or in a subject who has been administered no more than one induction therapeutic course. Some such embodiments include the administration of a NOX2 inhibitor, such as histamine dihydrochloride (HDC), in combination with a cytokine, such as interleukin-2 (L-2).

Abstract: Some embodiments of the methods and compositions provided herein relate to the treatment and amelioration of metastatic tumors and to the prevention of distant metastasis. In some embodiments, a metastatic tumor, such as a melanoma, can be treated by reducing the activity of NOX2 in a cell of a subject. In some embodiments, the activity of NOX2 can be reduced by administering a NOX2 inhibitor, such as histamine dihydrochloride (HDC).

Abstract: Disclosed herein include methods of delaying and preventing acute myeloid leukemia (AML) relapse in patients with mutant nucleophosmin 1 (NPM1) by co-administration of histamine, or derivatives thereof, and interleukin-2 (IL-2). In some embodiments, an unexpected delay in and/or prevention of relapse results in a surprising increase in leukemia- free survival rate and overall survival rate.

Abstract: An improved composition and method for reducing the formation of oxygen radicals in mononuclear phagocytes is disclosed. Also provided is a method of protecting NK cells from oxidative damage inflicted by radicals produced by mononuclear phagocytes by administering a histamine metabolite, N-alpha-methylhistamine dihydrochloride. Use of N-alpha-methylhistamine dihydrochloride for enhancing the NK cell response to IL-2 is likewise detailed.

Abstract: Method and composition for protecting tumorcidal lymphocytes including cytotoxic lymphocytes and NK cells from apoptosis and down regulation are provided. The method and composition include the administration of an effective amount of a PARP-1 inhibitor to a population of cytotoxic T lymphocytes and NK cells in the presence of monocytes or macrophages. In some embodiments, the method and composition additionally include the administration of a reactive oxygen metabolite (ROM) production or release inhibitory compound. Methods of treating cancer, viral diseases, and inflammatory diseases with a PARP-1 inhibitor are likewise provided.

Abstract: Disclosed is a method of promoting the maturation of monocytes comprising the administration of a reactive oxygen species (ROS) inhibitor or scavenger and at least one monocyte maturation-promoting agent. A composition for promoting the maturation of monocytes is likewise disclosed. The pharmaceutical composition includes a compound effective to promote the maturation of monocytes and a ROS inhibitor or scavenger combined in a pharmaceutically acceptable carrier.

Abstract: Disclosed is a method of promoting the maturation of monocytes comprising the administration of a reactive oxygen species (ROS) inhibitor or scavenger and at least one monocyte maturation-promoting agent. A composition for promoting the maturation of monocytes is likewise disclosed. The pharmaceutical composition includes a compound effective to promote the maturation of monocytes and a ROS inhibitor or scavenger combined in a pharmaceutically acceptable carrier.

Abstract: The present invention relates to methods of treating cancer in which histamine is administered in conjunction with other cancer therapies. The cancer therapy includes surgery, radiation, immunotherapy, the administration of an agent which enhances the humoral immune response of the patient or any combination thereof.

Abstract: The present invention relates to a method for preventing and/or reducing cellular and tissue damage caused by reactive oxygen metabolites (ROMs) released by phagocytic or endothelial cells in response to various disease states or pathologies. The methods of the present invention are useful in preventing and treating a variety of disease states or pathological situations in which ROMs are produced and released. The methods of the present invention contemplate reducing ROM-mediated damage by reducing the production and release of ROMs.

Abstract: Disclosed is a method of promoting the maturation of monocytes comprising the administration of a reactive oxygen species (ROS) inhibitor or scavenger and at least one monocyte maturation-promoting agent. A composition for promoting the maturation of monocytes is likewise disclosed. The pharmaceutical composition includes a compound effective to promote the maturation of monocytes and a ROS inhibitor or scavenger combined in a pharmaceutically acceptable carrier.

Abstract: Compositions and methods for treating a variety of conditions in which a reactive oxygen metabolite (ROM) inhibitor or scavenger is administered alone or in conjunction with additional agents. Such conditions include, cancer, viral diseases, and inflammatory diseases, for example.

Abstract: The present invention relates to a method for preventing and/or reducing cellular and tissue damage caused by reactive oxygen metabolites (ROMs) released by phagocytic or endothelial cells in response to various disease states or pathologies. The methods of the present invention are useful in preventing and treating a variety of disease states or pathological situations in which ROMs are produced and released. The methods of the present invention contemplate reducing ROM-mediated damage by reducing the production and release of ROMs.

Abstract: Methods for obtaining beneficial stable levels of circulating histamine are disclosed for use in methods for enhancing natural killer cell cytotoxicity and for elevating histamine levels in individuals in need thereof. In such methods, a beneficial level of circulating histamine is attained and an agent whose ability to enhance natural killer cell cytotoxicity is augmented by histamine is administered. Alternatively, stable beneficial levels of circulating histamine can be attained in subjects receiving chemotherapy or antiviral treatment. The invention may also be employed in treatments combining histamine, agents which enhance natural killer cell cytotoxicity, and chemotherapeutic agents. Optimization of the delivery of histamine and substances which induce the release of endogenous histamine are also disclosed.

Abstract: Described herein are compositions and methods for the treatment of microbial infection.

Abstract: The present invention relates to a method for facilitating activation of T-cells in a patient, comprising: identifying a patient in need of enhanced T-cell activity, administering an effective amount of a T-cell activating composition to the patient, and administering an effective amount of a compound that inhibits the production or release of intercellular reactive oxygen metabolites (ROM) to the patient. The present invention further relates to the use of H2-receptor agonists to augment the effectiveness of vaccines.

Abstract: The present invention relates to a method for preventing and/or reducing cellular and tissue damage caused by reactive oxygen metabolites (ROMs) released by phagocytic or endothelial cells in response to various disease states or pathologies. The methods of the present invention are useful in preventing and treating a variety of disease states or pathological situations in which ROMs are produced and released. The methods of the present invention contemplate reducing ROM-mediated damage by reducing the production and release of ROMs.

Abstract: The present invention relates to methods of treating cancer in which histamine is administered in conjunction with other cancer therapies. The cancer therapy includes surgery, radiation, immunotherapy, the administration of an agent which enhances the humoral immune response of the patient or any combination thereof.

Abstract: The present invention relates to methods of treating cancer in which histamine is administered in conjunction with other cancer therapies. The cancer therapy includes surgery, radiation, immunotherapy, the administration of an agent which enhances the humoral immune response of the patient or any combination thereof.