Chemically induced intracellular hyperthermia

Abstract

An invention relating to therapeutic pharmacological agents and methods to chemically induce intracellular hyperthermia and/or free radicals for the diagnosis and treatment of infections, malignancy and other medical conditions. The invention relates to a process and composition for the diagnosis or killing of cancer cells and inactivation of susceptible bacterial, parasitic, fungal, and viral pathogens by chemically generating heat, and/or free radicals and/or hyperthermia-inducible immunogenic determinants by using mitochondrial uncoupling agents, especially 2,4 dinitrophenol and, their conjugates, either alone or in combination with other drugs, hormones, cytokines and radiation.

1 - 54 . (canceled) 
   
   
       55 . A method for inducing intracellular hyperthermia in a subject comprising the step of administering an amount of a mitochondrial uncoupling agent sufficient to the subject to thereby induce whole body intracellular hyperthermia in the subject, wherein the induced intracellular hyperthermia in the subject is sufficient to treat a cancer in the subject 
   
   
       56 . The method of  claim 55  wherein the cancer is selected from the group consisting of prostate carcinoma, glioblastoma multiform, Kaposi's sarcoma, peritoneal carcinomatosis, and glioma and combinations thereof. 
   
   
       57 . The method of  claim 55 , wherein the mitochondrial uncoupling agent is 2,4-dinitrophenol and/or a conjugate thereof. 
   
   
       58 . The method of  claim 56 , wherein the mitochondrial uncoupling agent is 2,4-dinitrophenol and/or a conjugate thereof. 
   
   
       59 . The method of  claim 55 , further comprising the step of administering a second medication, wherein the second medication increases
 a) the overall metabolic rate of the subject,   b) the metabolic rate of a specific target tissue in the subject, and/or   c) free radical flux in the subject.   
   
   
       60 . The method of  claim 59 , wherein the second medication is selected from the group consisting of glucagon, arbutamine, dobutamine, vasopressin, glutamine, proline, octanoate, methylene blue (tetramethylthionine), ubiquinone, menadione, hematoprophyrin, polyunsaturated fatty acids, monounsaturated fatty acids and combinations thereof. 
   
   
       61 . The method of  claim 55 , wherein the induced intracellular hyperthermia is sufficient to cause the induction of heat shock proteins in a cell of the subject. 
   
   
       62 . The method of  claim 55 , further comprising the step of administering to the subject an anti-cancer agent selected from the group consisting of metholtrexate, mercaptopuorine, fluorouracil, cytarabine, thioguanine, azacitidine, etoposide (VP-16) and teniposide (VM-26), vincristine, vinblastine, paclitaxel, busulfan, cyclophosphamide, mechlorethamine, melphalan, altaretarnine, ifosfamide, cisplatin, dacarbazine, procarbazine, lomustine, carmustine, lomustine, semustine, chlorambucil, thiotepa, carboplatin; flutamide, prednisone, ethinyl estradiol, diethylstilbestrol, hydroxyprogesterone caproate, medroxyprogesterone, megestrolacetate, testosterone, fluoxymesterone, diiodothyroidine, triiodothyroidine, tetraiodothyroidine, aromatase inhibitor, amino glutethimide, octreotide, goserilin acetate, leuprolide, interferon alpha-2a, interferon alpha-2b, interferon-gamma, interferon-beta, interleukin-1, interleukin-2, interleukin-4, interleukin-10, anti-HER-2/neu humanized antibody, tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, macrophage-colony-stimulating factor, phenylacetates, retinoic acids, leukotrienes, thromboxanes, and combinations thereof. 
   
   
       63 . The method of  claim 55 , further comprising administering radiation to the subject.