Abstract: The present invention relates to methods for the treatment of metastatic cancer. Methods of treating metastatic cancer by administration of a set of drugs overcome multiple mechanisms of melphalan resistance and hypersensitize cancer cells to melphalan are described. The methods involve the administration of drug(s) that induce oxidative stress in cancer cells, in conjunction with melphalan on a defined schedule.

Abstract: The present invention relates to methods for the treatment of metastatic cancer. Methods of treating metastatic cancer by administration of a set of drugs overcome multiple mechanisms of melphalan resistance and hypersensitize cancer cells to melphalan are described. The methods involve the administration of drug(s) that induce oxidative stress in cancer cells, in conjunction with melphalan on a defined schedule.

Abstract: The present invention relates to methods and sets of drugs for the effective treatment of metastatic cancer and the administration of a set of drugs that overcome mechanisms of resistance to DNA-damaging agents, thereby sensitizing cancer cells to said DNA-damaging agents. The methods involve the administration of a set of drugs comprising melphalan, BCNU, hydroxocobalamin, and ascorbic acid. In a preferred embodiment, ethanol is also added to the set of drugs and bone marrow toxicity is reversed with an infusion of bone marrow stem cells. The methods also involve the depletion of GSH in tumors and the selective delivery of drugs to solid tumors. The methods also involve preventing the loss of catalase function and preventing oxidant-induced hemolysis and/or methemoglobin formation in subjects treated with oxidant drugs or agents that generate hydrogen peroxide, wherein said methods comprise the systemic administration of ethanol.

Abstract: The present invention relates to methods and sets of drugs for the effective treatment of metastatic cancer and the administration of a set of drugs that overcome mechanisms of resistance to DNA-damaging agents, thereby sensitizing cancer cells to said DNA-damaging agents. The methods involve the administration of a set of drugs comprising melphalan, BCNU, hydroxocobalamin, and ascorbic acid. In a preferred embodiment, ethanol is also added to the set of drugs and bone marrow toxicity is reversed with an infusion of bone marrow stem cells. The methods also involve the depletion of GSH in tumors and the selective delivery of drugs to solid tumors. The methods also involve preventing the loss of catalase function and preventing oxidant-induced hemolysis and/or methemoglobin formation in subjects treated with oxidant drugs or agents that generate hydrogen peroxide, wherein said methods comprise the systemic administration of ethanol.

Abstract: The present invention relates to methods for the treatment of metastatic cancer. Methods of treating metastatic cancer by administration of a set of drugs overcome multiple mechanisms of melphalan resistance and hypersensitize cancer cells to melphalan are described. The methods involve the administration of drug(s) that induce oxidative stress in cancer cells, in conjunction with melphalan on a defined schedule.

Abstract: The present invention relates to methods and sets of drugs for the effective treatment of metastatic cancer and the administration of a set of drugs that overcome mechanisms of resistance to DNA-damaging agents, thereby sensitizing cancer cells to said DNA-damaging agents. The methods involve the administration of a set of drugs comprising melphalan, BCNU, hydroxocobalamin, and ascorbic acid. In a preferred embodiment, ethanol is also added to the set of drugs and bone marrow toxicity is reversed with an infusion of bone marrow stem cells. The methods also involve the depletion of GSH in tumors and the selective delivery of drugs to solid tumors. The methods also involve preventing the loss of catalase function and preventing oxidant-induced hemolysis and/or methemoglobin formation in subjects treated with oxidant drugs or agents that generate hydrogen peroxide, wherein said methods comprise the systemic administration of ethanol.

Abstract: The present invention relates to methods for the treatment of metastatic cancer. Methods of treating metastatic cancer by administration of a set of drugs overcome multiple mechanisms of melphalan resistance and hypersensitize cancer cells to melphalan are described. The methods involve the administration of drug(s) that induce oxidative stress in cancer cells, in conjunction with melphalan on a defined schedule.

Abstract: The present invention relates to methods for the treatment of metastatic cancer. Methods of treating metastatic cancer by administration of a set of drugs overcome multiple mechanisms of melphalan resistance and hypersensitize cancer cells to melphalan are described. The methods involve the administration of drug(s) that induce oxidative stress in cancer cells, in conjunction with melphalan on a defined schedule.

Abstract: The present invention relates to method for the treatment or prevention and of proliferative eye diseases including but not limited to: age related macular degeneration associated proliferative retinopathy, proliferative diabetic retinopathy, proliferative vitreoretinopathy, posterior capsular opacification, scaring and fibrosis after glaucoma filtration surgery, uveal melanoma, and retinoblastoma. The method comprises contacting cells in the eye by means of intra-ocular injection or infusion, with a drug that irreversibly inhibits cellular proliferation without causing extensive tissue necrosis or cytotoxicity. In a preferred embodiment the drug is bizelesin.

Abstract: The present invention relates to the compositions, methods, and applications of a new approach to pattern recognition based targeting by which an exponential amplification of effector response can be specifically obtained at a targeted cells. The purpose of this invention is to enable the selective delivery of large quantities of an array of effector molecules to target cells for diagnostic or therapeutic purposes. The invention is comprised of two components designated as “Compound 1” and “Compound 2”: Compound 1 is comprised of a cell binding agent and a masked female adaptor. Compound 2 is comprised of a male ligand, an effector agent, and two or more masked female receptors. The male ligand is selected to bind with high affinity to the female adaptor. Compound 1 can bind with high affinity to the target cell and the female receptor can then be unmasked by an enzyme enriched at the tumor cell. The male ligand of Compound 2 can then bind to the unmasked female adaptor bound to the target cell.

Abstract: The present invention relates to the compositions, methods, and applications of a novel approach to selective cellular targeting. The purpose of this invention is to enable the selective delivery and/or selective activation of effector molecules to target cells for diagnostic or therapeutic purposes. The present invention relates to multi-functional prodrugs or targeting vehicles wherein each functionality is capable of enhancing targeting selectivity, affinity, intracellular transport, activation or detoxification. The present invention also relates to ultra-low dose, multiple target, multiple drug chemotherapy and targeted immunotherapy for cancer treatment.

Abstract: The present invention relates to the compositions, methods, and applications of a new approach to pattern recognition based targeting by which an exponential amplification of effector response can be specifically obtained at a targeted cells. The purpose of this invention is to enable the selective delivery of large quantities of an array of effector molecules to target cells for diagnostic or therapeutic purposes. The invention is comprised of two components designated as “Compound 1” and “Compound 2”: Compound 1 is comprised of a cell binding agent and a masked female adaptor. Compound 2 is comprised of a male ligand, an effector agent, and two or more masked female receptors. The male ligand is selected to bind with high affinity to the female adaptor. Compound 1 can bind with high affinity to the target cell and the female receptor can then be unmasked by an enzyme enriched at the tumor cell.

Abstract: Disclosed are novel prodrugs represented by the following structural formula: 1

Abstract: Disclosed are novel prodrugs represented by the following structural formula; Z is oxygen or sulfur; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a substituted benzyl group with one or more protected hydroxy or protected amine groups in the ortho or para positions, relative to the phosphate ester, which can be converted in vivo to a hydroxy or amino group. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.

Abstract: Disclosed are novel prodrugs represented by the following structural formula: Z is oxygen or sulfur; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a substituted benzyl group with one or more protected hydroxy or protected amine groups in the ortho or para positions, relative to the phosphate ester, which can be converted in vivo to a hydroxy or amino group. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.

Abstract: The composition and methods of synthesis of phosphorus prodrugs are described. These methods can be used to convert negatively charged phosphorus bearing drugs into neutrally charged; lipid soluble prodrugs which are able to passively diffuse into cells and into tissues in vivo. Prodrugs for a variety of antiviral and anti-leukemic agents are described.

Abstract: Disclosed are novel prodrugs represented by the following structural formula: ##STR1## Z is oxygen or sulfur; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a substituted benzyl group with one or more protected hydroxy or protected amine groups in the ortho or para positions, relative to the phosphate ester, which can be converted in vivo to a hydroxy or amino group. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.

Abstract: Disclosed are novel prodrugs represented by the following structural formulas: ##STR1## Z is oxygen or sulfur; n is 1 or 2; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a group which can be metabolized in vivo to a give a modified A such that the phosphoester bond (modified A)--O undergoes cleavage in vivo. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.

Abstract: The composition and methods of synthesis of phosphorus prodrugs are described. These methods can be used to convert negatively charged phosphorous bearing drugs into neutrally charged; lipid soluble prodrugs which are able to passively diffuse into cells and into tissues in vivo. Prodrugs for a variety of antiviral and anti-leukemic agents are described.

Abstract: The composition, synthesis, and applications of tumor associated protease activated prodrugs of phosphoramide mustard, isophosphoramide mustard and analogs with detoxification functionalities are described. These drugs release a cytotoxic phosphoramide mustard analog following activation by tumor associated proteases and esterases. The general structure for these drugs is: ##STR1## Wherein R1 is a beta-X-ethyl-amino group which may optionally bear substituents on the nitrogen or carbon atoms; wherein X is a good leaving group such as a halogen; R2 is a beta-X-ethyl-amino group which may optionally bear substituents on the nitrogen or carbon atoms; or an amino group (NH.sub.2) which may optionally be substituted. Wherein A is a benzyloxy derivative with one or more acyloxy or acylamino groups in para or ortho portions relative to the phosphoester; and wherein the acyloxy or acylamino groups are not (substituted or unsubstituted) p-guanidino-benzoyloxy groups or p-guanidino-benzoylamino groups.