Abstract: The present invention relates to a novel crystalline form of vinflunine, to a process for preparing it, and to its uses in the therapeutic field, in particular for treating cancer.

Abstract: Pre-treatment with ?,? unsaturated aryl sulfones protects normal cells from the cytotoxic side effects of two classes of anticancer chemotherapeutics. Administration of a cytoprotective sulfone compound to a patient prior to anticancer chemotherapy with a mitotic phase cell cycle inhibitor or topoisomerase inhibitor reduces or eliminates the cytotoxic side effects of the anticancer agent on normal cells. The cytoprotective effect of the ?,? unsaturated aryl sulfone allows the clinician to safely increasing the dosage of the anticancer chemotherapeutic.

Abstract: A stereoselective process for preparing 7-[(E)-t-butyloxyiminomethyl]-camptothecin (also known as gimatecan) is herein disclosed. With the addition of further dissolution and precipitation steps carried out in appropriate different solvent mixtures, four new crystalline forms of gimatecan are also obtainable by using the same stereoselective process.

Abstract: The present invention discloses and claims compositions, methods of treatment, and kits which cause an increase in time of survival in cancer patients, wherein the cancer either: (i) overexpresses thioredoxin or glutaredoxin and/or (ii) exhibits evidence of thioredoxin- or glutaredoxin-mediated resistance to one or more chemotherapeutic interventions. The present invention also discloses and claims methods and kits for the administration of said compositions to properly treat cancer patients. Additionally, the present invention discloses and claims methods and kits for quantitatively determining the level of expression of thioredoxin or glutaredoxin in the cancer cells of a cancer patient, methods of using those determined levels in the initial diagnosis and/or planning of subsequent treatment methodologies for said cancer patient, as well as ascertaining the potential growth “aggressiveness” of the particular cancer and treatment responsiveness of the particular type of cancer.

Abstract: Compounds of Formula (I) are described: in which the R1 group is as defined in the specification and includes the condensation of 7-t-butoxyiminomethylcamptothecin in position 20 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: The invention relates to novel esters and in particular to some novel esters of glucuronide prodrugs of anthracyclines having tunable water-solubility, their synthesis and use in tumor-selective chemotherapy. It appeared that in the final step in the synthesis of these prodrugs, i.e. the coupling of the glucuronide spacer moiety to the parent drug molecule, protection of the sugar hydroxyls is, surprisingly, no longer required. A process for the preparation of these unprotected sugar spacer moieties is also disclosed.

Abstract: Invented are novel 1H-imidazo[4,5-c]pyridin-2-yl compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

Abstract: The present invention provides for the identification of genes that are expressed in tumors that are responsive to a given therapeutic regime and whose expression correlates with responsiveness to that therapeutic regime. One or more of the genes of the present invention can be used as markers to identify patients that are likely to be successfully treated by a therapeutic regime.

Abstract: Aqueous-based, ready to use topotecan-containing formulations for parenteral use having extended stability are disclosed. The formulations are surprisingly free of precipitated degradation products such as 10-hydroxycamptothecin (10-HCPT) after periods of up to 1 year or greater.

Abstract: A recombinant vector capable of expressing MDR1 shRNA and thymidine kinase, and a use thereof. More specifically, provided is a recombinant vector capable of efficiently expressing MDR1 shRNA and thymidine kinase in a host cell, a transfectant cell comprising the same recombinant vector, a composition for treating neoplastic diseases, comprising the same recombinant vector, and a method for imaging of neoplastic lesions using the same recombinant vector. The recombinant vector of the present invention is capable of achieving efficient intracellular expression of MDR1 shRNA and a thymidine kinase-GFP fusion protein within the host cell and is therefore highly effective for combined therapy of anticancer drugs. Further, the recombinant vector of the present invention enables imaging of neoplastic lesions. Therefore, the recombinant vector of the present invention can be used in combination with other anticancer drugs for treatment of neoplastic diseases.

Abstract: This invention relates to the compounds of formula (I) shown below. Each variable in formula (I) is defined in the specification. These compounds can be used to treat a kinesin Eg5 protein-mediated disorder.

Abstract: An apparatus and system for delivering a lipophilic agent associated with a medical device including: a medical device, a first lipophilic agent capable of penetrating a body lumen, wherein the transfer coefficients of the first lipophilic agent is by an amount that is statistically significant of at least approximately 5,000, wherein the first lipophilic agent is associated with the medical device, wherein the first lipophilic agent/medical device is placed adjacent to said body lumen, and wherein a therapeutically effective amount of the first lipophilic agent is delivered to a desired area within a subject. Furthermore, the invention relates to a method for improving patency in a subject involving placement of a medical device in a body lumen for treating and/or preventing adjacent diseases or maintaining patency of the body lumen.

Abstract: The present invention provides fusion proteins comprising an extracellular domain of a VEGF receptor and a death ligand. The fusion proteins bind to VEGF and to death receptors on tumor cells thereby inhibiting VEGF activation of VEGF receptors and inducing apoptosis in the tumor cells. Fusion proteins of the present invention are useful for inducing apoptosis and cytotoxic effects in cells, treating cancer and diseases or disorders related to unregulated angiogenesis and/or vasculogenesis. Thus, this invention further provides methods for treating angiogenesis related diseases using the fusion proteins, polynucleotides encoding the fusion proteins, vectors containing the polynucleotides, pharmaceutical compositions and kits containing the fusion proteins or the polynucleotides encoding the fusion proteins.

Abstract: The present invention relates to 21-deoxymacbecin analogues that are useful, e.g. in the treatment of cancer, B-cell malignancies, malaria, fungal infection, diseases of the central nervous system and neurodegenerative diseases, diseases dependent on angiogenesis, autoimmune diseases or as a prophylactic pretreatment for cancer. The present invention also provides methods for the production of these compounds and their use in medicine, in particular in the treatment and or prophylaxis of cancer or B-cell malignancies.

Abstract: A method for treating contracture is provided that includes administering to a patient in need thereof a composition that includes a therapeutic agent effective in treating contracture. Compositions, devices, and kits for use in treating contracture are also described.

Abstract: Hydrated crystalline camptothecin esters, such as crystalline aliphatic ester hydrates of camptothecin, pharmaceutical compositions containing crystalline aliphatic ester hydrates of camptothecin, methods of treating a cancer or malignant tumor using the crystalline camptothecin ester hydrates and methods of making the same are described.

Abstract: Disclosed herein is a liposomal formulation that comprises a liposome and a liquid carrier. In the liposomal formulation, the liposome comprises a hydrophobic lactone drug and has an intraliposomal metal ion concentration higher than the metal ion concentration of the liquid carrier. Also disclosed herein is a method for active loading of a hydrophobic lactone drug into a liposome. The method includes preparing a liposome in the presence of a metal salt solution, an acid form of a counterion of the metal salt being membrane permeable, such that the liposome preparation contains entrapped metal ion. The method further includes forming a liposome with high intraliposomal pH by separating extravesicular metal salt solution from the liposome by exposing the liposome to a metal salt-free solution, resulting in diffusion of the acid form of the counterion out of the liposome and formation of an intraliposomal pH higher than that of the metal salt-free solution.

Abstract: The present embodiment of the invention is generally directed to compositions comprising suspensions of poorly water-soluble compounds recrystallized in nanoparticulate sizes ranging from 0.1 to 5 ?m. In addition, the embodiment of the invention is directed to methods for preparation and administration of these compositions to a patient for prevention and treatment of disease states.

Abstract: Provided is a liposome comprising a hydrophobic lactone drug and a cyclodextrin, wherein the liposome has an intraliposomal pH and cyclodextrin concentration such that upon administration of the liposome to a subject, the liposome exhibits a uniform release profile of the hydrophobic lactone drug. Also provided is a method of administering a hydrophobic lactone drug to a subject in need thereof. The method comprises administering a liposome to the subject in need, wherein the liposome comprises the hydrophobic lactone drug and a cyclodextrin. The liposome has an intraliposomal pH and cyclodextrin concentration such that upon administration of the liposome to the subject, the liposome exhibits a uniform release profile of the hydrophobic lactone drug.

Abstract: The invention relates to two novel crystalline form of Topotecan hydrochloride (Ia) Herein referred to as forms ? and ?, characterized by high purity and whose preparation is advantageous from the industrial point of view. Form ? can be in fact conveniently prepared starting from 10-hydroxy-camptothecin, whereas form ? can be prepared starting from form ?.

Abstract: A chemotherapeutic composition can be configured for subcutaneous administration for preferential intralymphatic accumulation while also providing a therapeutic systemic concentration that is not toxic. The composition can include a pharmaceutically acceptable carrier, and a nanoconjugate configured for preferential intralymphatic accumulation after subcutaneous administration. The nanoconjugate can include a nanocarrier configured for preferential intralymphatic accumulation after subcutaneous or interstitial administration, and a plurality of chemotherapeutic agents coupled to the nanocarrier. The nanoconjugate can have a dimension of about 10 nm to about 50 nm. Also, the nanoconjugate can be loaded with the chemotherapeutic agents from about 10% to about 50% w/w. The nanocarrier can be a hyaluronan polymer of about 3 kDa to about 50 kDa. Alternatively, the nanocarrier can be a dendrimer.

Abstract: The present invention provides compositions and uses of an ascomycin macrolactam for the treatment of an unwanted ocular condition occurring in a patient undergoing treatment with a therapeutically active agent for the treatment of cancer.

Abstract: This invention relates to pulsatile dose administration of gossypol, a gossypol-related compound or pharmaceutical compositions thereof for treating diseases, disorders and conditions responsive to gossypol or gossypol-related compound, inhibiting the activity of anti-apoptotic Bcl-2 family proteins, inducing apoptosis in cells and increasing the sensitivity of cells to inducers of apoptosis.

Abstract: A method for the preparation of a compound of general Formula: or pharmaceutically acceptable derivatives and salts, racemates, isomers and/or tautomers thereof comprising cyclizing an azomethine ylide of general Formula: wherein, A is a cyclic or non-cyclic group; Z is a carbon or a heteroatom; n is selected from 0, 1, 2 or 3; W, X and Y may be the same or different and each are selected from hydrogen; optionally substituted alkyl, alkenyl, alkynyl, amino, alkoxy, alkenoxy, alkynoxy, aryl, alkylthio, heterocyclyl; carboxy, carboxy ester, carboxamido, acyl, acyloxy, mercapto, halogen, nitro, sulfate, phosphate, cyano and optionally protected hydroxy; or W and X, together with the nitrogen and carbon atoms to which they are attached, form a saturated or unsaturated nitrogen containing heterocyclic group which may be optionally substituted or optionally fused to a saturated or unsaturated carbocyclic group, aryl group or heterocyclic group is provided.

Abstract: A transdermal therapeutic system for administering lipophilic, poorly water-soluble and/or sparingly skin-permeable pharmaceutical active substances. The active substance is present in a multi-component enhancer system consisting of 4 components and each component of the multi-component enhancer system is selected from a different one of the substance groups: a) terpenes, b) cyclic glucitol ethers, c) medium-chain triglycerides of capric and caprylic acid and/or of linoleic acid; and d) longer-chain alcohols having a chain length of 8 or more carbon atoms.

Abstract: Modified or attenuated therapeutic viruses in combination with a chemotherapeutic agent, and methods for administering therapeutic viruses in combination with a chemotherapeutic agent to a subject for controlling viral titer, are provided. The combination of a therapeutic virus and chemotherapeutic agent can be used in methods of treating diseases, such as proliferative and inflammatory disorders, including as anti-tumor agents. The combination can also be used as a preventive measure or as a treatment to reduce or eliminate symptoms associated with oncolytic viral therapy.

Abstract: The present disclosure relates to a kind of sodium alginate microsphere vascular embolus that contains water-soluble drug and preparation and application thereof. The embolus preparation falls into dry microsphere type and wet one that are made of degradable materials. The drug carrier can be sodium alginate, human serum albumin, chitosan or sodium hyalurate, solidifying and forming microsphere together with calcium ion solution under presence of static charge. The microsphere can have a diameter in the range of 20-1000 ?m and can be divided into a wide variety of sizes in case of need. The present disclosure adopts raw materials that are good at mechanical strength, bio-compatibility, bio-degradability and stability.

Abstract: The present invention provides releasably-linked indenoisoquinoline polymer conjugates. Methods of making the conjugates and methods of treating mammals using the same are also disclosed.

Abstract: In one aspect, the present invention provides a composition and a kit comprising a combination of topoisomerase inhibitor and PARP inhibitor for treatment of cancer. In another aspect, the invention provides a method of treating cancer comprising administering to a subject a combination of topoisomerase inhibitor and PARP inhibitor. In particular, the invention provides compositions and methods for treating cancer in a subject by inhibiting a poly-ADP-ribose polymerase and a topoisomerase, as well as providing formulations and modes of administering such compositions.

Abstract: The present invention relates to methods of determining colorectal cancer status in a subject. The invention further relates to kits for determining colorectal cancer status in a subject. The invention further related to methods of identifying biomarker for determining colorectal cancer status in a subject.

Abstract: A method for preventing and/or treating peripheral neuropathies induced by the administration of an anticancer agent of the family of platin compounds, taxanes, epothilone class, vinca alkaloids, said method comprising the administration in a co-ordinated manner to a subject suffering from said peripheral neuropathies, or expected to suffer from said peripheral neuropathies, an effective amount of acetyl L-carnitine or of a pharmaceutically acceptable salt thereof. In case of prevention, acetyl L-carnitine is administered to a subject, in view of the need of a treatment with an anticancer agent, immediately before or immediately after surgical removal of the tumor, but in any case before the administration of the anticancer agent. Acetyl L-carnitine can enhance the supportive effect of physiological NGF during chemotherapy-induced neuropathy, thus avoiding the problem of the local and general side effects of the exogenous administration of NGF which are a major problem of this neuroprotective strategy.

Abstract: In one aspect, the present invention provides a method of treating breast cancer that is negative for at least one of ER, PR, or HER2, comprising administering to a subject at least one PARP inhibitor. In another aspect, the present invention provides a method of treating breast cancer comprising administering to a subject at least one PARP inhibitor in combination with at least one anti-tumor agent.

Abstract: This invention is related to a pharmaceutical combination that contains a Casein kinase 2 (CK2) peptide inhibitor (termed P15) along with the standard chemotherapeutic drugs used in cancer treatment and which are administered together, separated or sequentially. The chemothearapeutic drugs include cisplatin, taxol, alkaloids from Vinca, 5-fluorouracil, doxorubicin, cyclophosphamide, etoposide, mitomicin C, imatinib, iressa and velcade (vortezomib). The synergism between the P15 peptide and the anticancer drugs achieves an efficient concentration of each cytostatic drug in the combination which is from 10- to 100-fold lower than that for each cytostatic drug alone. The pharmaceutical combination described in this invention exhibits lower toxicity compared to that reported by the anticancer therapeutics and therefore, it represents a crucial advantage for its use in cancer therapy.

Abstract: The invention provides a medical device comprising a hydrophobic analog of a medicament known to inhibit cell proliferation and migration. The invention also provides a method of treating a narrowing in a body passageway comprising placing an implantable medical device comprising a hydrophobic analog of a medicament known to inhibit cell proliferation and migration. The medicaments can be incorporated within or coated on the device. The invention further provides hydrophobic analogs of medicaments known to inhibit cell proliferation and migration.

Abstract: Preventive or therapeutic agents for pancreatic cancer, ovarian cancer, or liver cancer of the present invention comprise a water-soluble prodrug represented by formula 1 described below, or a pharmaceutically acceptable salt, or a hydrate or solvate of the prodrug or pharmaceutically acceptable salt, (wherein, R1 represents a hydrogen atom, or a C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or a divalent group comprising a sulfonyl group, and Y represents a residue of a compound represented by Y—OH comprising an alcoholic hydroxyl group, wherein said Y—OH is a camptothecin, a taxane, or an anticancer nucleotide).

Abstract: The invention relates to the use of enzymatic inhibitors of h-PRUNE and to screening method for the prevention and treatment of the metastases of tumours overexpressing h-PRUNE thereof and to the diagnostic kit for the prognosis of said metastases thereof.

Abstract: A liposome contains an active agent and has a gel-phase lipid bilayer membrane comprising phospholipid and a surface active agent. The phospholipids are the primary lipid source for the lipid bilayer membrane and the surface active agent is contained in the bilayer membrane in an amount sufficient to increase the percentage of active agent released at the phase transition temperature of the lipid bilayer, compared to that which would occur in the absence of the surface active agent. The surface active agent is present in the lipid bilayer membrane so as to not destabilize the membrane in the gel phase.

Abstract: The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the enzyme Thimet oligopeptidase, or TOP. Also disclosed are methods of designing prodrugs by utilizing TOP-cleavable sequences within the conjugate and methods of treating patients with prodrugs of the invention.

Abstract: The invention provides a composition for delivering active agents through transmucosal administration, more particularly through the buccal mucosa. The composition is a unique transmucosal disk (10) which has two compartments (14) and (18); the compartments consist of at least one active agent and at least one mucoadhesive agent and both the compartments are adapted to be in contact with the mucosal membrane. The invention also provides for transmucosal administration of an active agent and method of treatment of diseases in a subject in need of such treatment.

Abstract: The present invention relates to compounds, compositions for use in reversing multidrug resistance in cancer cells, process for the preparation thereof and their uses in treating cancers. More particularly, the present invention relates to 3?,4?-aromatic acyloxy substituted 7,8-pyranocoumarins compounds for use in reversing P-glycoprotein overexpression mediated multidrug resistance in cancer cells, pyranocoumarins containing compositions, process for the preparation thereof and their uses in treating cancers.

Abstract: Hydrated crystalline camptothecin esters, such as crystalline aliphatic ester hydrates of camptothecin, pharmaceutical compositions containing crystalline aliphatic ester hydrates of camptothecin, methods of treating a cancer or malignant tumor using the crystalline camptothecin ester hydrates and methods of making the same are described.

Abstract: The invention provides for compositions and methods for predicting an individual's responsitivity to cancer treatments and methods of treating cancer. In certain embodiments, the invention provides compositions and methods for predicting an individual's responsitivity to chemotherapeutics, including salvage agents, to treat cancers such as ovarian cancer. The invention also provides reagents, such as DNA microarrays, software and computer systems useful for personalizing cancer treatments, and provides methods of conducting a diagnostic business for personalizing cancer treatments.

Abstract: The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer based multifunctional compositions and systems for use in disease diagnosis and therapy (e.g., cancer diagnosis and therapy). The compositions and systems comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and monitoring the response to therapy of a cell or tissue (e.g., a tumor).

Abstract: Formulations and methods for their preparation including a hydrogel including a crosslinked matrix comprising a polymer, and a one or more liposomes containing a therapeutic agent.

Abstract: The invention provides methods and compositions for use in treating diseases associated with excessive cellular proliferation, such as cancer.

Abstract: The present invention provides novel tricyclic spiro-oxathiine naphthoquinone derivatives, a synthetic method for making the derivatives, and the use of the derivatives to induce cell death and/or to inhibit proliferation of cancer or precancerous cells. The naphthoquinone derivatives of the present invention are related to the compound known as ?-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho(1,2-b)pyran-5,6-dione).

Abstract: Compounds of the following formula: wherein X is H or substituted with with at least one X being substituted; and halo is fluorine, chlorine, bromine, iodine; and stereoisomers and conjugable analogs thereof.

Abstract: Nanoparticles made from a select group of lipids and optionally containing a therapeutically active agent are employed in pharmaceutical compositions for delivery to targeted tissues and/or cells for the treatment or diagnosis of such diseases as cancer.

Abstract: The novel C10-modified camptothecin analogs, and pharmaceutically-acceptable salts thereof, of the present invention: (i) possess potent antitumor activity (i.e., in nanomolar or subnanomolar concentrations) for inhibiting the growth of human and animal tumor cells in vitro; (ii) are potent inhibition of Topoisomerase I; (iii) lack of susceptibility to MDR/MRP drug resistance; (iv) require no metabolic drug activation: (v) lack glucuronidation of the A-ring or B-ring; (vi) reduce drug-binding affinity to plasma proteins; (vii) maintain lactone stability; (viii) maintain drug potency; and (ix) possess a low molecular weight (e.g., MW<600).

Abstract: The novel C7-modified camptothecin analogs, and pharmaceutically-acceptable salts thereof, of the present invention: (i) possess potent antitumor activity (i.e., in nanomolar or subnanomolar concentrations) for inhibiting the growth of human and animal tumor cells in vitro; (ii) are potent inhibition of Topoisomerase I; (iii) lack of susceptibility to MDR/MRP drug resistance; (iv) require no metabolic drug activation: (v) lack glucuronidation of the A-ring or B-ring; (vi) reduce drug-binding affinity to plasma proteins; (vii) maintain lactone stability; (viii) maintain drug potency; and (ix) possess a low molecular weight (e.g., MW<600).