Abstract: The invention relates to the use of arsenic compounds to treat a variety of neoplastic diseases. The present invention encompasses the administration to a mammal of arsenic in the form of a salt, complex, organic compound or ionic solution to treat tumors of epithelial tissue, connective tissue, central nervous system, lymphoid tissue, hematopoietic cells and tumors associated with oncogenic viruses. This invention also encompasses the treatment of hematopoietic disorders in mammals by the administration of one or more arsenic compounds to said mammal. Further, the arsenic compounds may be used to treat metastatic neoplastic diseases.

Abstract: The invention relates to the use of treosulfan as a conditioning agent before allogenic transplantation of bone marrow or haematopoietic stem cells, whereby treosulfan is administered, either as single effective agent, or in combination with other chemotherapetic agents or immunosuppressant agents.

Abstract: The present invention provides aqueous Ifosfamide compositions and a process for their preparation, in which the compositions have a reduced toxicity over and above the concomitant use of the uroprotective agent, Mesna. Aqueous Ifosfamide compositions can be prepared at concentrations as high has 1,1000 mg/ml.

Abstract: A method of immunotherapy to treat cancer or a synergistic anti-cancer treatment by administering an effective amount of a natural cytokine mixture (NCM), an effective amount of cyclophosphamide (CY), or an effective amount of indomethacin (INDO), wherein the NCM, CY, or INDO are administered singly or in combinations thereof. An anti-metastatic treatment method by promoting differentiation and maturation of immature dendritic cells in a lymph node; allowing presentation thereof; and preventing development of metastasis. A method of using an NCM as a diagnostic skin test for predicting treatment outcome. A method of pre-treating dendritic cells (DC) and a method of treating monocyte defects characterized by sinus histiocytosis or a negative NCM skin test. Compositions and methods for eliciting an immune response to endogenous or exogenous tumor antigens.

Abstract: The invention relates to the use of arsenic compounds to treat a variety of neoplastic diseases. The present invention encompasses the administration to a mammal of arsenic in the form of a salt, complex, organic compound or ionic solution to treat tumors of epithelial tissue, connective tissue, central nervous system, lymphoid tissue, hematopoietic cells and tumors associated with oncogenic viruses. This invention also encompasses the treatment of hematopoietic disorders in mammals by the administration of one or more arsenic compounds to said mammal. Further, the arsenic compounds may be used to treat metastatic neoplastic diseases.

Abstract: Glycolytic inhibitors are useful in the treatment of solid tumors by attacking anaerobic cells at the center on the tumor. 2-deoxyglucose, oxamate and various analogs thereof are identified as having a natural selective toxicity toward anaerobic cells, and will significantly increase the efficacy of standard cancer chemotherapeutic and radiation regiments as well as new protocols emerging with anti-angiogenic agents.

Abstract: The present invention provides a formulation for inhibiting metastasis which includes 150–600 units of IL-2, a nonsteroidal anti-inflammatory drug (NSAID), and cyclophosphamide. The present invention further provides a formulation for inhibiting metastasis that includes IL-1, IL-2, IL-6, IL-8, ?-IFN and TNF-?.

Abstract: Compounds of Formula I, their preparation and uses are described: wherein: M and V are cis to one another and MH is cytarabine; the 5? oxygen of said cytarabine is attached to the phosphorus; V is 4-pyridyl; and pharmaceutically acceptable prodrugs and salts thereof.

Abstract: The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.

Abstract: The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.

Abstract: Compounds of the structure I: are useful for treating bacterial growth, wherein E is selected from the group consisting of B, P, and S, T1 and T2 are each independently selected from the group consisting of O, NR, and CH2, where R?H or C1–C8 alkyl, or C1–C8 oxoalkyl, and L is selected from the group consisting of ethylene, propylene, and four to six-membered alicyclic and aromatic rings, provided that structure I does not include AI-2-borate. The compounds may be used to treat bacterial infections in human beings and to regulate biofilm formation. Pharmaceutical compositions comprising one or more such compounds are useful for treating bacterial infections in human beings.

Abstract: The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.

Abstract: The invention relates to a therapeutic composition for broad spectrum dermal disease and in particular, to a composition comprising principal lipid components of skin, preferably having about 30 to 90% by weight of a carrier for applying to skin; 0.01 to 5.0% by weight of sphingolipid long-chain base; 0.001 to 1.0% by weight of lysophosphatidic acid; and 1 to 40% by weight of organic or inorganic additives. The composition is useful for the treatment and improvement of atopic dermatitis, psoriasis, acne, ichthyosis, infectious dermatitis, pruritus, erythema derived from pruritus, vulnus, chapping of skin and ulcer, etc.

Abstract: The present invention provides therapeutic compositions containing lysophosphatidic acids, methods for making the compositions, and methods of use thereof.

Abstract: Novel FBPase inhibitors of the formula I are useful in the treatment of diabetes and other conditions associated with elevated blood glucose.

Abstract: Cyclic glycerophosphates and analogs thereof (CGs) are shown to exert neutral promoting activities in target cells. Such activities include promotion of neuronal outgrowth, promotion of nerve growth, provision of dopaminotrophic supporting envrionment in a diseased portion of the brain, prevention of nerve degeneration and nerve rescue. These activities of the CGs render them useful for treatment of various disorders including but not limited to mental disorders such as, for example, schizophrenia, dementia or disorders resulting in learning disablities. In addition, these CGs may be used for the treatment of neurodegenerative conditions such as Altzheimer's diesease, Parkinson's disease, conditions resulting from exposure to harmful environmental factors or resulting from a mechanical injury. The CGs may also be used to treat an individual suffering from a primary neurodengenerative condition in order to prevent or reduce the appearance of secondary degeneration in additional nerves (“nerve rescue”).

Abstract: The invention relates to the use of arsenic compounds to treat a variety of neoplastic diseases. The present invention encompasses the administration to a mammal of arsenic in the form of a salt, complex, organic compound or ionic solution to treat tumors of epithelial tissue, connective tissue, central nervous system, lymphoid tissue, hematopoietic cells and tumors associated with oncogenic viruses. This invention also encompasses the treatment of hematopoietic disorders in mammals by the administration of one or more arsenic compounds to said mammal. Further, the arsenic compounds may be used to treat metastatic neoplastic diseases.

Abstract: Antineoplastic drug modulators are described. The specific modulators referred to are propargylamines which can enhance the cytotoxic effects of antineoplastic drugs on cancer cells while protecting normal cells from damage. The propargylamine modulators can be used to increase the selectivity and effectiveness of conventional antineoplastic drugs, to reduce the unwanted side-effects of cancer chemotherapy, to improve effectiveness of cancer chemotherapy, to improve treatment of cancers for which treatment is otherwise ineffective, to improve therapy of cancers otherwise unresponsive or poorly responsive due to drug-resistance and/or toxicity limited treatment regimens and to render effective chemotherapy for previously untreatable cancers.

Abstract: Novel compounds according to formula I n is 0, 1, 2 or 3; X represents hydroxamic acid (CONHOH), carboxylic acid, phosphonic acid, acetylthiomethyl group or a mercaptomethyl group; R2, R10 and R11 independently represent hydrogen or (C1-8)alkyl, (C2-6)alkenyl, (C3-8)cycloalkyl, aryl(C0-6)alkyl or heteroaryl(C0-6)alkyl, all of which may optionally be substituted; R3 and R4 independently represent hydrogen, hydroxy or alkoxy; provided that if A, A′, Z and R5 are all bonds, and s and t are both 0 (zero), then R6 is different from hydrogen, and that at least one of R3, R4, R10 and R11 is different from hydrogen; or a salt, hydrate or solvate thereof; pharmaceutical compositions comprising said compound; therapeutical methods comprising administering said compounds; and the use of said compounds in the manufacture of medicaments.

Abstract: The present invention relates to peptide-like compounds, e.g. aminocarboxylic acid amide derivatives, and to methods of using same to stimulate cells of the immune system, bone marrow and other organs. The present compounds can be used to enhance vaccination, increase synthesis of and enhance function of blood cell components and enhance anti-neoplastic effects of various agents. The compounds of the invention can be used to produce a variety of further pharmacologic effects.

Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.

Abstract: The invention concerns a novel approach for treating cystic fibrosis using, in particular, anti-cancer chemotherapy. For the treatment of cystic fibrosis it proposes the use of at least one product which when administered to a patient brings about the expression or overexpression of an ABC carrier compound, in particular glutathione carrier. Preferably, the products used are anti-cancer products whose administration brings about the expression of MRP and/or MDR protein. The invention is also applicable to the treatment of rheumatoid polyarthritis or asthma. More specifically, the compounds are selected among cyclophosphamide, aclarubicin, doxorubicin, daunorubicin, epirubicin, idarubicin, zorubicin, pirabucin, colchicine, videsine, vinorelbine, vincristine, binblasine, azithromycin, erythromycin, ifosmamide, N-acetyl cysteine, N-acetyl lysine and/or a CFTR protein fragment comprising the NBF1 domain.

Abstract: A composition of glutathione and selenium, as a selenoamino acid or selenium yeast extract and an epidermal growth factor in a topical carrier and method of using the composition to reduce and repair skin damage, resulting from aesthetic (exfoliation and chemical peels) and surgical (laser and other therapies) procedures and other chemical and thermal burns to the cutaneous tissues.

Abstract: This invention features methods and compositions of combination therapy suitable for treating and preventing epithelial lesions. Lesions are treated or prevented by combining trefoil peptide therapy with another medically useful therapeutic agent. Suitable therapeutics for combination therapy with a trefoil peptide included chemotherapeutics, particularly orally administered chemotherapeutics, analgesic, antibiotic, and anti-inflammatory agents. Useful trefoil peptides include the naturally occurring trefoil peptides intestinal trefoil factor, spasmolytic polypeptide (SP), and pS2, as well as non-naturally occurring peptides that contain a trefoil domain.

Abstract: The present invention relates to non-lethal methods of conditioning a recipient for bone marrow transplantation. In particular, it relates to the use of nonlethal doses of total body irradiation, total lymphoid irradiation, cell type-specific or cell marker-specific antibodies, especially antibodies directed to bone marrow stromal cell markers or the CD8 cell marker, cytotoxic drugs, or a combination thereof. The methods of the invention have a wide range of applications, including, but not limited to, the conditioning of an individual for hematopoietic reconstitution by bone marrow transplantation for the treatment of hematologic malignancies, hematologic disorders, autoimmunity, infectious diseases such as acquired immunodeficiency syndrome, and the engraftment of bone marrow cells to induce tolerance for solid organ, tissue and cellular transplantation.

Abstract: The present invention provides a stable, sterile, pharmaceutical product that consists essentially of lyophilized ifosfamide and solutions thereof. The lyophilized ifosfamide of the present invention is suitable for pharmaceutical use, and can be stored in one or more aseptically sealed containers. The present invention further provides a method of producing lyophilized ifosfamide, which method includes freezing a sterile solution of ifosfamide and subjecting it to a primary drying stage. The primary drying stage includes applying a vacuum to remove solvent while raising the temperature to a primary drying temperature, to produce a first intermediate. The first intermediate is subjected to a secondary drying stage, which includes applying a vacuum to further remove solvent while raising the temperature to a secondary drying temperature, to produce the pharmaceutical product.

Abstract: Novel cyclo azaphospha hydrocarbons according to formula I are provided. The compounds are useful as metalloprotease inhibitors.

Abstract: The present invention provides therapeutic compositions containing lysophosphatidic acids, methods for making the compositions, and methods of use thereof.

Abstract: Disclosed and claimed are prodrugs activated by catalytic proteins, such as enzymes and catalytic antibodies. The invention comprehends such prodrugs, as well as haptens, to elicit catalytic antibodies to activate the prodrugs. The prodrugs are useful as cytotoxic chemotherapeutic agents; e.g., as antitumor agents.

Abstract: The invention relates to use of (a) compounds of phosphorus containing at least partly lipophilic organic radicals together with (b) urea and/or urea derivatives in selected quantity ratios of (a) to (b) as a soil additive for biologically controlling plant-parasitic soil nematodes by strengthening the correspondingly antagonistic soil potential, more particularly by strengthening the growth of antagonistic and/or nematicidal rhizosphere bacteria and/or corresponding mycorrhiza strains—and at the same time strengthening the growth of cultivated plants in soil. The multicomponent mixtures which strengthen bacterial growth are preferably introduced into the region of the plant roots in the form of an aqueous preparation using plant-compatible emulsifiers before and/or during plant growth. Components (a) and (b) are used in such quantity ratios that the ratio by weight of C to N is no higher than 6:1 and preferably no higher than 5:1.

Abstract: This invention relates to combination chemotherapy, particularly involving vitamin D or a derivative thereof. In one aspect, the invention provides a method of killing a cell by first administering to the cell vitamin D (or a derivative) and subsequently administering to the cell a cytotoxic agent. Where this strategy is applied to an intact tumor, the present invention provides a method of retarding the growth of the tumor by first administering vitamin D (or a derivative) to the tumor and subsequently administering the cytotoxic agent. A further aspect of the invention concerns a method of treating prostate cancer within a patient by co-administration of vitamin D (or a derivative) and a glucocorticoid to the patient. In yet a further aspect, the invention provides an improved method of treating a patient with vitamin-D involving the adjunctive administration of zoledronate.

Abstract: The present invention provides pro-micelle compositions comprising a pharmaceutically active agent encapsulated with a membrane of esterified C12-C18 fatty acids. In the mammalian intestine, exposure to C12-C18 fatty acids results in conversion of the pro-micelle to a stable micelle that effectively delivers the pharmaceutically active agent to the systemic circulation. The present invention further provides methods of making and using such compositions.

Abstract: The invention provides methods of treating neoplasia using combinations of target cell-specific replication competent adenoviral vectors and chemotherapy, radiation therapy or combinations thereof. The adenoviral vectors are target cell-specific for the particular type of neoplasia for which treatment is necessary and the combination with the chemotherapy and/or radiation leads to synergistic treatment over existing adenoviral therapy or traditional chemotherapy and radiation therapy.

Abstract: The invention relates to the use of a combination of ifosfamide and carnitine, in particular L-carnitine, for the production of tumour pharmaceuticals having decreased side effects. The results show clearly that the side effect produced by ifosfamide (damage to the proximal tubule of the kidney) is antagonized in animals by L-carnitine. It was furthermore possible to show that the antitumour action of ifosfamide is not affected in combination with L-carnitine. The combination also caused no new side effects in the animals.

Abstract: New methods for the treatment of human disease are provided. IGFBP-3 is administered together with a co-administered agent to subjects having disease, thereby alleviating the symptoms of the disease, under conditions where administration of IGFBP-3 alone at the maximum practicable dose has no measurable beneficial effect on the disease condition.

Abstract: Hematopoietic chimerism induces donor-specific tolerance to solid organ grafts. The clinical application of this technique is limited by the morbidity and mortality of conventional bone marrow transplantation (BMT). Conditioning for engraftment is nonspecific, utilizing myeloablation plus nonspecific immunosuppression. In the present study we have characterized which cells in the recipient hematopoietic microenvironment prevent allogeneic marrow engraftment. Mice defective in production of &agr;&bgr;-TCR cells, &ggr;&dgr;-TCR cells; &agr;&bgr;- plus &ggr;&dgr;-TCR cells; CD8 cells and CD4 cells were transplanted with MHC-disparate allogeneic bone marrow. In normal mice, 500 cGy total body irradiation (TBI) plus cyclophosphamide (200 mg/kg) on day +2 is required for engraftment of allogeneic hematopoietic stem cells (HSC).

Abstract: This invention relates to substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors, to pharmaceutical compositions comprising such compounds, and to methods of using these compounds for treating viral infection. A representative compound of the invention is the compound of formula: wherein R22 and R23 are allyl.

Abstract: The present invention provides therapeutic compositions containing lysophosphotidic acids, methods for making the compositions, and methods of using the compositions in the preservation and treatment of organs.

Abstract: The present invention relates to a method of increasing the sensitivity of neoplastic cells to chemotherapeutic agents by using a virus, a method of treating proliferative disorders with a virus and chemotherapeutic agents, and a method for preventing a neoplasm from developing drug resistance to chemotherapeutic agents. The virus is preferably a reovirus.

Abstract: A method for enhancing the efficacy of chemotherapy in the treatment of cancer in animals, particularly humans, is provided wherein isocoumarin derivatives that exhibit unique chemopotentiation properties are employed in a combination treatment with chemotherapy.

Abstract: A method of preparing a human recipient for a graft from a human which includes: administering donor peripheral blood progenitor cells to the recipient, and providing a minimally ablative.

Abstract: The present invention provides compositions and methods for treating proliferative disorders using combination therapies of lometrexol and other therapeutically active agents. The methods include administration of lometrexol with one or more therapeutically active agents where lometrexol and the therapeutically active agent(s) are delivered in a single composition, where they are administered in separate compositions in a simultaneous manner, where lometrexol is administered first, followed by the therapeutically active agent(s), as well as where the therapeutically active agent(s) is delivered first, followed by lometrexol. In preferred embodiments, the therapeutically active agent(s) has antiproliferative properties.

Abstract: The invention provides compounds and compositions of containing intracellular inhibitors of the mucin MUC-1. These intracellular MUC-1 inhibitors are exemplified by protein-based inhibitors that contain a targeting and/or an internalization domain, and by antisense nucleic acids. These inhibitors are useful in methods of treating autoimmune disorders.

Abstract: Fosfomycin or a pharmaceutically acceptable salt thereof has been found to have an action of lowering the serum glucose level and is recognized to be useful as an orally administrable remedy for treating diabetes. It has further been found that the serum glucose level-lowering action of fosfomycin or its salt can be enhanced synergistically and significantly when forfomycin is administered in association with vanadyl sulfate and the like. Therefore,the composition comprising fosfomycin or its salt and vanadyl sulfate or the like is useful as an orally administrable remedy for treating diabetes.

Abstract: The present invention relates generally to a method for the treatment or prophylaxis of animals including humans suffering from or predisposed to breast cancer or other related cancers which comprises the use of cytokines and/or functionally active derivatives, hybrids and/or analogs thereof and to pharmaceutical compositions comprising same as therapeutic agents. In particular, but not exclusively, the present invention is directed to the use of cytokines which are ligands of members of the haemopoietin receptor super family or their derivatives, hybrids or analogues as therapeutic agents. The present application also contemplates breast cancer therapies and methods of suppressing growth of normal breast cells or breast cancer cells by the use of one or more cytokines optionally in combination with other therapeutic agents as well as the use of agonists or antagonists of cytokine activity. Particularly preferred are oncostatin M (OSM) and leukemia inhibitory factor (LIF).

Abstract: The invention is based on the discovery that angiogenic vessels have heterogeneous surface charge and that cationic liposomes actually target human tumor blood vessels only in irregularly shaped patches. The invention thus features methods for delivering therapeutic compounds to angiogenic vascular endothelial surfaces using a mixture, or “cocktail”, of positively charged and neutral liposomes. The new methods can be used to target multiple regions on the same tumor vessel and/or clusters of vessels within the same tumor. Liposomes with different chemical and/or physical properties (e.g., charge, stability, solubility, diameter) can be delivered simultaneously, and can target tumor vessels and other angiogenic vessels with greater efficiency compared to cationic liposomes alone.

Abstract: Fosfomycin or a pharmaceutically acceptable salt thereof has been found to have an action of lowering the serum glucose level and is recognized to be useful as an orally administrable remedy for treating diabetes. It has further been found that the serum glucose level-lowering action of fosfomycin or its salt can be enhanced synergistically and significantly when fosfomycin is administered in association with vanadyl sulfate and the like. Therefore, the composition comprising fosfomycin or its salt and vanadyl sulfate or the like is useful as an orally administrable remedy for treating diabetes.

Abstract: This invention is to provide a compound of the formula: wherein R1 is an optionally substituted 5- to 6-membered ring; W is a divalent group of the formula: wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted C, N or O atom, and the ring B is an optionally substituted 5- to 7-membered ring; Z is a chemical bond or a divalent group; R2 is (1) an, optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, etc., or a salt thereof, which is useful for antagonizing MCP-1 receptor.

Abstract: Prodrugs of formula I, their uses, their intermediates, and their method of manufacture are described: 1

Abstract: A method for enhancing the efficacy of chemotherapy and/or radiation in the treatment of cancer in animals, particularly humans, is provided wherein certain isocoumarin derivatives which exhibit unique radiosensitization activity and/or chemopotentiation properties are employed in a combination treatment with ionizing radiation and/or chemotherapy.