Abstract: CXCR3 agonists, including natural CXCR3 ligands, promote bone marrow regeneration, increase peripheral white blood cells, and increase survival if administered prior to treatment of a subject with chemotherapy or radiotherapy. Similar effects are obtained by administering an CXCR3 antagonists following chemotherapy radiotherapy. Compositions and methods are presented for the treatment of cancer and bone marrow diseases.

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).

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: Microparticle carriers, particularly protein-encapsulated microbubbles, are used to deliver antiproliferative drugs to target sites in a subject. In particular, antirestenotic drugs are delivered to areas of vascular injury for treatment or prevention of hyperproliferative disease, e.g. stenosis, in blood vessels; and antineoplastic drugs are targeted to tumor sites.

Abstract: The present invention involves the use of 2,4-disulfonyl phenyl tert-butyl nitrone (2,4-ds-PBN) in the treatment and prevention of gliomas. The 2,4-ds-PBN may be used alone or combined with other traditional chemo- and radiotherapies and surgery, to treat or prevent glioma occurrence, recurrence, spread, growth, metastasis, or vascularization.

Abstract: The invention is related to water-soluble products and pharmaceutical formulations in solid or liquid form mainly for parenteral use. They consist of or comprise a therapeutically active substance (having low aqueous solubility and a substantial binding affinity to plasma proteins) and a plasma protein fraction in controlled aggregation state, whereby the said active substance and the said protein fraction are bound to each other by way of non-covalent bonds. It also covers processes for the preparation of the product and pharmaceutical formulation by dissolving the water-insoluble active substance in a water-miscible, pharmaceutically acceptable solvent, combining said solution with the aqueous solution of a plasma protein fraction in controlled aggregation state whereby a true solution is obtained containing the said active substance and the said protein fraction bound together by way of non-covalent bonds.

Abstract: A pharmaceutical composition in the form of a gelatin capsule comprising a pharmaceutically acceptable acid.

Abstract: A first aspect of the invention relates to a combination comprising 2?-cyano-2?-deoxy-N4-palmitoyl-1-?-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof. A second aspect relates to a pharmaceutical product comprising (i) 2?-cyano-2?-deoxy-N4-palmitoyl-1-?-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and (ii) a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof, as a combined preparation for simultaneous, sequential or separate use in therapy.

Abstract: This invention relates to compositions and methods utilizing a chemotherapeutic drug and 6-bromoindirubin3?-oxime (BIO) for the treatment of cancer, including glioblastoma multiforme. The present invention demonstrates that BIO works synergistically with chemotherapeutic drugs to increase the cytotoxic effects of these drugs in glioma cells.

Abstract: The use of a compound of formula (I), is disclosed in treating and/or preventing 5 chemotherapy-induced peripheral neurotoxicity (CIPN). The invention includes pharmaceutical compositions wherein the compound of formula (I) is present in a mixture with anticancer agents. An improved anticancer treatment with reduced CIPN-related side effects is also provided.

Abstract: A 5(S)-(2?-hydroxyethoxy)-20(S)-camptothecin diasterisomer is described which is a better inhibitor of topoisomerase I than either the diastereoisomeric mixture 5(RS)-(2?-hydroxyethoxy)-20(S)-camptothecin, or the 5(R)-(2?-hydroxyethoxy)-20(S)-camptothecin diastereoisomer. Pharmaceutical compositions of the 5(S)-(2?-hydroxyethoxy)-20(S)-camptothecin diastereoisomer are also described as are methods of using the compound for the inhibition of topoisomerase I and for the treatment of cancer.

Abstract: New methods of treating Ras associated cancer, and especially for treating cancer that is resistant or refractory to other treatment methods, including resistant or refractory to treatment with C225 and/or CPT-11, are provided. The new methods employ PEG-conjugated 7-ethyl-10-hydroxycampothecin, alone, or in combination with other art-known anticancer agents or modalities.

Abstract: The present invention includes methods and compositions for the treatment and prevention of protozoal parasitic infections utilizing Diindolylmethane-related indoles. Additive and synergistic interaction of Diindolylmethane-related indoles with other known anti-parasitic and pro-apoptotic agents is believed to permit more effective therapy and prevention of protozoal parasitic infections. The methods and compositions described provide new treatment of protozoal parasitic diseases of mammals and birds including malaria, leishmaniasis, trypanosomiasis, trichomoniasis, neosporosis and coccidiosis.

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-hydroxy-camptothecin to patients in need thereof.

Abstract: A subclass of camptothecin derivatives is disclosed to be useful for the preparation of a medicament for the treatment of a cancer or tumor pathology selected from the group consisting of head and neck carcinoma, pancreas carcinoma, melanoma, bladder carcinoma, mesothelioma and epidermoid skin carcinoma.

Abstract: The present invention is directed towards lasonolide derivatives, methods of inducing premature chromosome condensation using lasonolide derivatives, and methods of treating disorders, such as cancer, in a subject, the method comprising administering to the subject a lasonolide derivative.

Abstract: Disclosed are new substituted pyrazole and triazole compounds of Formula (I) and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the derivatives together with pharmaceutically acceptable carriers, and uses thereof:

Abstract: A method of treating a hyperproliferative disorder, including a cancer, in a subject in need of such treatment, comprising administering to said subject a pharmaceutical combination containing a treatment effective amount of: (a) a vitamin A derivative (i.e., a retinoid), or a pharmaceutically acceptable salt thereof, and an inhibitor of microtubule structure or function; or (b) a combination containing fenretinide (i.e., N-(4-hydrophenyl) retinamide, 4-HPR) and ABT-751 (i.e., N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide). Vitamin A derivatives that may be useful for this invention according to (a) include, but are not limited to, all-trans-retinoic acid, 13-cis-retinoic acid, and fenretinide. Microtubule inhibitors that may be useful for this invention according to (a) include, but are not limited to, inhibitors of the Vinca binding domain (e.g., vincristine, vinblastine, vinorelbine, and cryptophycin 52), inhibitors of the Taxane domain (e.g.

Abstract: A combination therapy for treating patients suffering from proliferative diseases or diseases associated with persistent angiogenesis is disclosed. The patient is treated with a camptothecin derivative and one or more chemotherapeutic agents selected from a microtubule active agent; an alkylating agent; an anti-neoplastic anti-metabolite; a platin compound; a topoisomerase II inhibitor; a VEGF inhibitor; a tyrosine kinase inhibitor; an EGFR kinase inhibitor; an mTOR kinase inhibitor; an insulin-like growth factor I inhibitor; a Raf kinase inhibitor; a monoclonal antibody; a proteasome inhibitor; a HDAC inhibitor; and ionizing radiation.

Abstract: A group of novel phenanthroindolizidine alkaloid compounds as shown and their use in treating cancer. Also disclosed are methods of using phenanthroindolizidine alkoid compounds in suppressing NO and TNF-? production, inhibiting MEKK1 activity and cyclooxygenase II expression, and treating NO-related disorders.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Abstract: In one aspect, the present invention provides a method of treating uterine cancer, endometrial cancer, or ovarian cancer, comprising administering to a subject at least one PARP inhibitor. In another aspect, the present invention provides a method of treating uterine cancer, endometrial cancer, or ovarian cancer, comprising administering to a subject at least one PARP inhibitor in combination with at least one anti-tumor agent.

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 nanoparticle composition comprising a camptothecin derivative, solid polyethyleneglycol and an anti-associative agent, and the process for preparing the same. Specifically, the present invention provides a composition comprising a nanoparticle of the camptothecin derivative, which is prepared by solid-dispersing the poorly water soluble camptothecin derivative in polyethyleneglycol and dissolving the solid dispersions in an aqueous solution containing an anti-associative agent. The composition of the present invention stabilizes the camptothecin derivative lactone form in body fluid for effective anticancer activity.

Abstract: New substituted heterocyclic compounds, compositions containing them, and methods of using them for the inhibition of Raf kinase activity are provided. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.

Abstract: The invention describes a vitamin receptor binding drug delivery conjugate, and preparations therefor. The drug delivery conjugate consists of a vitamin receptor binding moiety, a bivalent linker (L), and a drug. The vitamin receptor binding moiety includes vitamins, and vitamin receptor binding analogs and derivatives thereof, and the drug includes analogs and derivatives thereof. The vitamin receptor binding moiety is covalently linked to the bivalent linker, and the drug, or the analog or the derivative thereof, is covalently linked to the bivalent linker, wherein the bivalent linker (L) includes components such as spacer linkers, releasable linkers, and heteroatom linkers, and combinations thereof. Methods and pharmaceutical compositions for eliminating pathogenic cell populations using the drug delivery conjugate are also described.

Abstract: The present invention provides a method of promoting bone growth in a subject in need thereof, by administering to the subject a therapeutically effective amount of a compound of Formula I. The compounds include the salts, hydrates and isomers thereof. The present invention also provides methods for the treatment of renal disease and cancer.

Abstract: The invention features conjugates of therapeutic or cytotoxic agents and biologically active peptides and methods of use thereof.

Abstract: New camptothecin derivatives with the following structure of the formula (I), their use and the pharmaceutical compositions containing the same. The compounds of the present invention have good anti-tumor activities and good solubility in water, and can be used in development of medicines.

Abstract: An injectable polymer-lipid blend is provided. The blend may provide a localized drug delivery system for a pharmaceutically active agent. The blend may be prepared from a chitosan-based material, fatty acid and phospholipid. The chitosan-based material may be a water soluble chitosan derivative. The fatty acid may be a fatty acid or a fatty aldehyde, such as laurinaldehyde, having an acyl chain length of C8-C16. The rheological properties of the blend relates to the ratio of the components and to the acyl chain length of the fatty acid. The injectable system is well suited for the delayed release of pharmaceutically active agents in the treatment of cancer and other diseases requiring localized drug delivery.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell.

Abstract: The present invention is directed to methods for detecting the presence of genetic polymorphisms that correlate with altered gene expression. More specifically, the present invention is directed to methods for detecting the genetic polymorphisms located in the UGT1A1 promoter. The invention also provides methods for optimizing drug dosages based upon the presence of the polymorphisms. The invention further provides methods of predicting sensitivity to xenobiotics and diagnostic kits for detecting genetic polymorphisms.

Abstract: The invention relates to disorazoles of the general formula I, which are employed as medicaments, preferably for the treatment of oncoses, in particular in the case of pharmaceutical resistance to other active compounds and in the case of metastasizing carcinoma. The possible uses are not restricted to oncoses.

Abstract: Pyridonecarboxamide derivatives, pharmaceutical compositions which contain the same and methods for treating hyper-proliferative disorders and angiogenesis disorders using the same.

Abstract: Disclosed are compositions comprising a hydrophobic active agent, a polymer and a reconstitution enhancing agent. Reconstitution of the lyophilized form of the compositions takes less time than in the absence of the enhancing agent.

Abstract: It has now been found that the p53 pathway is inactivated in ocular cancers such as retinoblastoma. As such, the present invention is a method for inducing ocular cancer cell death using a p53 activator. In particular embodiments, the p53 activator blocks the interaction between DM2 or DMX and p53. As the p53 activator induces ocular cancer cell death, a method for preventing or treating ocular cancer is also provided.

Abstract: The invention discloses a method for classification of cancer in an individual having contracted cancer. The method of classification involves the determination of microsatellite status and a prognostic marker by examining gene expression patterns. The invention also relates to various methods of treatment of cancer. Additionally, the present invention concerns a pharmaceutical composition for treatment of cancer and uses of the present invention. The invention also relates to an assay for classification of cancer.

Abstract: The present invention provides a system presenting site-specific accumulation through a ligand that specifically targets a receptor overexpressed on the surface of specific cells within a target organ, like, for example, tumor cells and/or vascular cells of tumor blood vessels. Moreover, this invention provides a method where, upon internalization of the previous-mentioned system by the target cells, triggered release at a high rate of the associated agent takes place, permitting efficient intracellular delivery and, thus, increased concentration of the transported cargo at the target site. Overall, this invention provides a method for the diagnosis, prevention and treatment of human diseases and disorders.

Abstract: The present invention is directed to liposomal compositions comprising a camptothecin, which are optimized to reduce camptothecin degradation and/or precipitation of camptothecin degradation products in the external medium. The invention further provides improved methods of formulating liposomal camptothecins, kits comprising liposome-encapsulated camptothecins, and methods of using the same to treat a variety of diseases and disorders, including cancer.

Abstract: A pharmaceutical product comprising lyophilised polymer matrix including a biologically active compound, of particular utility for embolisation, having improved rehydration properties is packaged in an airtight package under vacuum.

Abstract: A new class of imidazolines as 4-position esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma, etc.), antibacterial agents, and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-?B as well as potent activity against the Gram (+) bacterium. The compositions are also useful for treating autoimmune diseases and for inhibiting rejection of organ and tissue transplants.

Abstract: The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. Examples of such anti-cancer agents or treatments include doxorubicin, cisplatin, or ionizing radiation. The present invention also provides a pharmaceutical composition comprising an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier.

Abstract: Compounds are disclosed with the general formula in which the groups are as defined in the description here below and characterized by the presence of polyamine substituents on the imine/oxime residue, such amine groups being in turn protected by suitable protective groups. Said compounds are endowed with potent topoisomerase I inhibiting activity and therefore are useful as medicaments for the treatment of tumors and viral and parasite infections.

Abstract: The present invention includes compositions and methods for treating a patient with cardiac hypertrophy by providing the patient with an effective amount of a Calmodulin kinase kinase inhibitor that is sufficient to treat cardiac hypertrophy.

Abstract: The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor of Formula (I) (e.g. OSI-906). Examples of such anti-cancer agents or treatments include doxorubicin, cisplatin, and ionizing radiation. The present invention also provides a pharmaceutical composition comprising an anti-cancer agent that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor of Formula (I), in a pharmaceutically acceptable carrier. The present invention also provides a method of identifying tumor cells that will respond most favorably to treatment with a combination of an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor.

Abstract: The invention provides compositions and methods for the targeted, in particular, pH targeted, delivery of pharmaceutically active agents in mammals. The compositions comprise pH sensitive diblock copolymers, which permit the release of the pharmaceutically active agent when exposed to an environment having a particular pH. The compositions are particularly useful for the oral delivery of water insoluble pharmaceutically active agents.

Abstract: A 5(S)-(2?-hydroxyethoxy)-20(S)-camptothecin diasterisomer is described which is a better inhibitor of topoisomerase I than either the diastereoisomeric mixture 5(RS)-(2?-hydroxyethoxy)-20(S)-camptothecin, or the 5(R)-(2?-hydroxyethoxy)-20(S)-camptothecin diastereoisomer. Pharmaceutical compositions of the 5(S)-(2?-hydroxyethoxy)-20(S)-camptothecin diastereoisomer are also described as are methods of using the compound for the inhibition of topoisomerase I and for the treatment of cancer.

Abstract: A crystalline form of 5(S)-(2?-hydroxyethoxy)-20(S)-camptothecin diastereoisomer of 5(RS)-(2?-hydroxyethoxy)-20(S)-camptothecin is described that is characterized by having an X-ray powder diffraction pattern comprising one or more peak intensities expressed in degrees 2? that are selected from the group consisting of 7.2±0.1, 9.4±0.1, 11.02±0.1, 12.00±0.1, 14.54±0.1, 15.2±0.1, 18.92±0.1, 21.86±0.1, 22.74±0.1 and 26.42±0.1. Methods of making and using the compound are also described.

Abstract: Azole compounds containing carbamoyl group and pharmaceutically useful salts thereof are described. The compounds are effective anticonvulsants which are used in the treatment of disorders of the central nervous system, especially as anxiety, depression, convulsion, epilepsy, migraine, bipolar disorder, drug abuse, smoking, ADHD, obesity, sleep disorder, neuropathic pain, stroke, cognitive impairment, neurodegeneration, stroke and muscle spasm.

Abstract: The present invention is directed to methods and compositions for determining the presence or absence of polymorphisms within an ABCC2, UGT1A1, and/or SLCO1B1 gene and correlating these polymorphisms with activity levels of their gene products and making evaluations regarding the effect on their substrates, particularly those substrates that are drugs. In addition, there are methods and compositions of evaluating the risk of an individual for developing toxicity or adverse event(s) to an ABCC2, UGT1A1, and/or SLCO1B1 substrate. In some embodiments, the invention concerns methods and compositions for determining the presence or absence of ABCC2 3972C>T variant and predicting or anticipating the level of activity of ABCC2 and determining dosages of an ABCC2 drug substrate, such as irinotecan, in a patient.