Abstract: A camptothecin/polymer dual phase drug release system is described that is stable in both liquid and lyophilized states. The polymer contains acetals and/or ketals.

Abstract: Disclosed is a crystalline form of irinotecan hydrochloride (I) and processes for the preparation thereof from crude irinotecan hydrochloride or another polymorphic form of irinotecan. Said crystalline form is particularly suitable for industrial use, because it is easily filtered and possesses characteristics of high stability and purity.

Abstract: The present invention relates to a method of stabilizing a low molecular weight compound in a cationic liposome, wherein said compound has a low solubility in a lipid membrane and/or a low permeability across a lipid membrane. Preferrably, the compound is modified in order to increase lipid membrane solubility and/or lipid membrane permeability. After delivery of the cationic liposome to a target site, particularly a target site in an organism, the modification is reversed and the low molecular weight compound may enact its desired activity.

Abstract: Disclosed is a novel crystalline form of topotecan monohydrochloride pentahydrate, which is a pentahydrate of 10-[(dimethylamino)methyl]4-ethyl-4,9-dihydroxy-1H-pyrano[3?,4?:6,7]indolizino[1,2-b]quinoline-3,14(4H, 12H)dione monohydrochloride, corresponding pharmaceutical compositions, methods preparation and/or use thereof to treat anti-viral and/or cancer related diseases.

Abstract: The present application is generally directed to compounds, compositions and methods of combination therapy for the treatment of neoplastic disorders.

Abstract: Novel indoleamine 2,3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.

Abstract: The present invention relates to pharmaceutical compositions comprising a topoisomerase I inhibitor including, but not limited to, a camptothecin derivative.

Abstract: The invention provides a combination comprising an ancillary compound (e.g.

Abstract: Compound of formula (I): wherein: R1, R2, R3, R4, R5, R80, R90, R81, R91, Alk and G are as defined in the description. Medicinal products containing the same which are useful in the treatment of cancer diseases.

Abstract: Compound of formula (I): wherein: R1, R2, R3, R4, R5, R80, R90, R81, R91, Alk, Alk?, X, X? and G are as defined in the description. Medicinal products containing the same which are useful in the treatment of cancer diseases.

Abstract: The present invention relates to a method for identifying a drug candidate for enhancing expression of p21ctpl/wafl in a human patient suffering from a medical condition that can be treated by enhancing expression of p21C?l/wafl. The method includes (a) providing a cell line comprising a nucleic acid sequence that comprises a p21ctpl/wafl promoter operationally ligated to a reporter domain; (b) exposing the cell line to a compound; and (c) identifying a compound that induces expression of the reporter domain. The compound that induces expression of the reporter domain is a drug candidate for treating a medical condition that can be treated by enhancing expression of p21cipl/wafl.

Abstract: This invention provides a method for a method for optimizing the regimen for the administration of chemotherapeutic agents. The method comprises administration of a selenium compound to an individual, monitoring the modulation of tumor vessel maturation (TVM) to identify an optimal time for administration of a chemotherapeutic agent. This invention also provides a method to determine whether or not a tumor is likely to be a responder to chemotherapy. The method comprises administration of a selenium compound to an individual and determining whether or not an increase in TVM is observed. An increased TVM following administration of selenium is an indication that the tumor will likely respond the chemotherapy.

Abstract: The invention concerns uses of anti-KL? agents, and detection of KL? and/or FGF19 and/or FGFR4.

Abstract: The present invention relates to methods of treatment of non-Hodgkin's lymphomas. The present invention includes administering polymeric prodrugs of 7-ethyl-10-hydroxycamptothecin to patients in need thereof.

Abstract: Disclosed are antitumor combinations of VEGF inhibitors with Irinotecan and the use thereof in the treatment of neoplastic diseases.

Abstract: There is provided a new use of microspheres comprising a water-insoluble, water-swellable polymer which is anionically charged at pH7, and electrostatically associated with the polymer, in releasable form, a cationically charged chemotherapeutic agent, in the manufacture of a composition for use in the treatment of a brain tumour, wherein in the treatment the composition is introduced into the brain and the chemotherapeutic agent is released from the microspheres, wherein the microspheres, when equilibrated in water at 37° C., comprise at least 40 wt % water based on weight of polymer plus water. Compositions comprising the microspheres and methods for the treatment of brain tumours are also provided.

Abstract: A compound selected from those of formula (I): wherein: B1, B2 represent carbon or nitrogen, X, Y, X1 and Y1 represent a group selected from hydrogen, halogen, hydroxy, alkoxy, nitro, cyano, trihaloalkyl and NRaRb wherein Ra and Rb are as defined in the description, R1 represents hydrogen or alkyl, R2 represents a group selected from hydrogen, alkyl, —OR?a, —NR?aR?b, —O-Ta-OR?a, —NR?a-Ta-NR?aR?b, NR?a—C(O)-TaH, —O—C(O)-TaH, —O-Ta-NRa?Rb?, —NR?a-Ta-OR?a, —NR?a-Ta-CO2R?a and —NR?a—C(O)-Ta-NR?aR?b wherein R?a, R?b, R?a and Ta are as defined in the description, R3, R4 represent hydrogen or alkyl, A represents a group of formula —CH(R5)—CH(R6)—, —CH?C(R7)—, —C(R7)?CH—, —C(O)—CH(R8)— or —CH(R8)—C(O)— wherein R5, R6, R7 and R8 are as defined in the description, its isomers, N-oxides, and addition salts thereof with a pharmaceutically acceptable acid or base, and medicinal products containing the same which are useful in the treatment of cancer.

Abstract: The present invention relates to the use of pharmaceutically acceptable zinc salts, preferably water soluble zinc salts alone or optionally, in combination with one or more of a protein pump inhibitor (PPI), H2 blocker, anti-H. pylori antibiotic/antimicrobial, cytoprotective agent or a combination agent as otherwise described herein for providing fast action with optional long duration effect in reducing gastric acid secretion, raising the pH of the stomach during resting phase as well as decreasing the duration of stomach acid release during a secretagogue phase and for treating conditions including gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), Zollinger-Ellison syndrome (ZE disease), ulcer disease, and gastric cancer, as well as preventing or reducing the likelihood of ulcer disease.

Abstract: 8-quinolinol (8Q) and derivatives thereof for use in the treatment of proliferative diseases such as cancer, in particular slow metabolizing quiescent cancer stem cells.

Abstract: The compound 4-{4-[({3-tert-Butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}-carbamoyl)amino]-3-chlorohenoxy}-N-methylpyridine-2-carboxamide and alternatives forms thereof (e.g., salts, hydrates, solvates, prodrugs, polymorphs and metabolites); pharmaceutical compositions which contain them and methods for treating cancer using them.

Abstract: Methods for treatment of sexual dysfunction in men and women using combinations of phosphodiesterase (PDE) type 5 inhibitors and l-deprenyl or propargylamine compounds are described. Methods of reducing the dosage and preventing the side effects of PDE type 5 inhibitors are also described. The methods comprise administering a therapeutically effective amount of l-deprenyl or propargylamine compounds (also called monoamine oxidase [MAO] inhibitors) in combination with PDE inhibitors. Stimulation of nitric oxide production and vasodilation by l-deprenyl and propargylamine compounds augments the actions of PDE inhibitors or other drugs and methods used in the treatment of sexual dysfunction. The composition described here enhances the actions of PDE inhibitors primarily by increasing the generation of cyclic GMP by stimulating the nitric oxide pathway and secondarily by providing several additional benefits such as enhanced dopamine activity.

Abstract: Compounds, compositions, and methods of using such compounds to modulate apoptosis including IAP antagonists are provided herein. Compositions including mimetics of the invention and, optionally, secondary agents, may be used to treat proliferative disorders such as, cancer and autoimmune diseases.

Abstract: The present invention relates to new podophyllotoxin inhibitors of topoisomerase II, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention relates to a prodrug which comprises at least two different pharmaceutically and/or diagnostically active compounds independently bound by cleavable linkers and a protein-binding moiety which is capable of binding to carrier a molecule.

Abstract: The present invention relates generally to a method of treating a neoplastic condition and to agents useful for same. More particularly, the present invention is directed to a method of facilitating the treatment of a metastatic neoplastic tumour in a localised manner by effecting the exposure of neoplastic cell intra-cellular molecules, preferably intra-nuclear molecules, suitable for use as a therapeutic target. The co-localisation of tumour cells and metastases to discrete tissue locations thereby renders the method of the present invention useful in terms of the delivery of bystander-based therapy.

Abstract: This invention relates to the field of protein tyrosine kinases and inhibitors thereof. In particular, the invention relates to inhibitors of JAK-2, pharmaceutical compositions of the compounds for inhibiting JAK-2, methods of inhibiting JAK-2 in a cell, comprising contacting a cell in which inhibition of JAK-2 is desired with a compound or pharmaceutical composition comprising a compound according to the invention. The also comprises methods of treating a disease or condition that involves JAK-2 comprising administering to a patient a pharmaceutical composition comprising a compound according to the invention.

Abstract: An object of the invention is to provide a camptothecin compounds-containing aqueous pharmaceutical preparation which can be produced without heating and in which camptothecin compounds are dissolved in a stable state. The invention provides a camptothecin compound-containing aqueous pharmaceutical preparation, containing the following ingredients (a) to (c): (a) a camptothecin compound; (b) a phosphoric acid salt; and (c) phosphoric acid.

Abstract: The invention relates to a compound of the formula (I) in which: R1, R2 and R3 are independently a methoxy group optionally substituted by one or more fluorine atoms; R4 is a hydrogen atom; R5 and R6 are identical and each represent a hydrogen or fluorine atom; A is a cycle selected from the group including aryl and heteroaryl groups, wherein said groups can be substituted.

Abstract: The use of dimiracetam in the treatment of chronic pain is disclosed. At doses higher than those previously disclosed in relation with its cognition enhancing activity (i.e. amelioration of learning and memory), dimiracetam was able to completely revert hyperalgesia or allodynia associated with several animal models of chronic pain. Dimiracetam showed high activity in iatrogenic neuropathies associated with antiviral and chemotherapeutic drug treatments and in painful conditions caused by osteoarthritis. In addition, dimiracetam was devoid of toxicity even at doses 10-fold higher than the highest therapeutic dose. The possibility of treating such debilitating pathologies with a highly effective and essentially non-toxic compound is therefore disclosed.

Abstract: A four arm-polyethylene glycol-7-ethyl-10-hydroxycamptothecin conjugate, such as, is disclosed. Methods of making the conjugates and methods of treating mammals using the same are also disclosed.

Abstract: Novel camptothecin derivatives having antitumor activity, the processes for the preparation thereof, the use thereof as antitumor drugs and pharmaceutical compositions containing them.

Abstract: The present invention relates to a method for prolonging longevity using and NPC1L1 antagonist. The present invention also provides a method for reducing weight in an individual who consumes a high-fat diet using an NPC1L1 antagonist.

Abstract: The invention provides vinblastine derivatives represented by the following formula 1 or their physiologically acceptable salts, their preparation, use and pharmaceutical compositions comprising the said derivatives. The said vinblastine derivatives show inhibiting activities against tumor cell lines and can be used as medicaments for treating malignant tumors.

Abstract: The present invention provides methods for detecting and treating cancer. In some embodiments, levels of ISG15 are determined, and topoisomerase I and II inhibitors as well as other DNA-damaging agents plus agents that increase the expression of ISG15 are selected and administered.

Abstract: Methods for treating neoplasm, tumors and cancers, using one or more tumor treating drug carriers, haptens and anticancer drugs, alone or in combination with other antineoplastic agents or treatments, are provided. Also provided are compositions, and kits containing the composition for affecting the therapy.

Abstract: The present invention provides a pharmaceutical composition comprising a combination of an Flt-3 inhibitor and at least one compound, the said pharmaceutical composition wherein an Flt-3 inhibitor is an indazole derivative represented by Formula (I) (wherein R1 represents substituted or unsubstituted aryl, or the like) or a pharmaceutically acceptable salt thereof, the said pharmaceutical composition wherein an Flt-3 inhibitor is a pyrimidine derivative represented by Formula (II) [wherein —X—Y—Z— represents —O—CR17?N— (wherein R17 represents a hydrogen atom, lower alkyl, or the like), R15 represents —NR22aR22b (wherein R22a and R22b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like), and R16 represents —NR24aR24b (wherein R24a and R24b may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like), or the like] or a pharmaceutically acceptable salt thereof, or the like.

Abstract: A method of treating a condition in a subject in need thereof, comprising administering a calcium/calmodulin dependency kinase kinase (CaMKK) inhibitor in a treatment-effective amount. Conditions which may be treated include obesity (particularly adult obesity), insulin resistance (including high fat diet-induced insulin resistance), hyperglycemia (including hyperglycemia accompanying obesity), diabetes, etc.

Abstract: The present invention relates, in general, to neuroblastoma and, in particular, to a method of treating neuroblastoma tumors, including refractory neuroblastoma tumors. The invention also relates to compounds and compositions suitable for use in such a method.

Abstract: The present disclosure generally relates to therapeutic nanoparticles. Exemplary nanoparticles disclosed herein may include about 1 to about 20 weight percent of a vinca alkaloid; and about 50 to about 99 weight percent biocompatible polymer.

Abstract: Compounds of Formula (I) are described in which the R1 group is as defined in the specification and includes the condensation of the camptothecin molecule in position 7 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors ?v?3 and ?v?5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

Abstract: Methods of treating, preventing and/or managing cancer as well as and diseases and disorders associated with, or characterized by, undesired angiogenesis are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active ingredient. The invention further relates to methods of reducing or avoiding adverse side effects associated with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy which comprise the administration of an immunomodulatory compound. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

Abstract: The present invention relates to a pharmaceutical composition for the treatment of cancer as well as methods of treatment of cancer that are based on the finding that certain benzimidazole based anti-cancer agents can be used in combination with a second anti-cancer agent to achieve desirable therapeutic outcomes. More specifically the present invention relates to a pharmaceutical composition including a benzimidazole based anti-cancer agent and a second anti-cancer agent. The invention also relates to methods of treatment of cancer including administration of a benzimidazole based anti-cancer agent and a second anti-cancer agent to a patient in need thereof.

Abstract: A method of therapeutic treatment of CNS disorders using local convection enhanced delivery.

Abstract: The invention refers to the use of a cytokine antagonist which modulates the expression and/or the function of a cytokine, particularly a Th2 helper cell cytokine, in a cell and causes the down-regulation of anti-apoptotic proteins in said cell through the cytokine modulation for sensitizing cells for apoptosis. In particular, the cells that can be treated with the cytokine antagonists are drug-resistant cancer cells which fail to undergo apoptosis.

Abstract: The use of 7-ter-butoxyiminomethylcamptothecin is described in the preparation of a medicament useful for the treatment of uterine neoplasms, particularly cancer of the endometrium and of the neck of the womb.

Abstract: The present invention is related to 10,20-di-O ester derivatives of camptothecin and pharmaceutical formulations thereof. The compounds and pharmaceutical formulations of the present invention possess increased biological life span and bioavailability and reduced toxicity, while maintaining anti-cancer activity.

Abstract: The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group —(O)n—R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxyg

Abstract: This invention relates to pharmaceutical compositions consisting of a semisynthetic derivative of vinca alkaloid, stable at room temperature, in which said derivative is present in the form of a freeze dried product obtained in the presence of at least one carbohydrate.

Abstract: The present invention provides a method for treating cancer. The method involves the administration of an HSP90 inhibitor and an antimitotic, where the combined administration provides a synergistic effect. In one aspect of the invention, a method of treating cancer is provided where a subject is treated with a dose of an HSP90 inhibitor in one step and a dose of an antimitotic in another step. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an HSP90 inhibitor and subsequently treated with a dose of an antimitotic. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an antimitotic and subsequently treated with a dose of an HSP90 inhibitor.

Abstract: The present invention provides methods and formulations for optimizing the anti-cancer and anti-HIV activities of a camptothecin drug, including camptothecin and its related analogs including 9-aminocamptothecin and 9-nitrocamptothecin. The invention involves methodologies and formulations that limit human serum albumin-mediated reduction of the anti-cancer and anti-HIV effects of the camptothecins, and the methods and formulations provide combination therapies in which binding of the camptothecin agent to human serum albumin can be modulated by the administration of a competing agent that also binds human serum albumin. Reduced camptothecin drug binding to human serum albumin can result in elevated camptothecin free drug levels and thus improve the effectiveness of treatment regimens involving these drugs. Further agents such as methotrexate and AZT can also be used in cancer and HIV-positive patients employing camptothecin drugs.