Abstract: The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent.

Abstract: In one aspect, the present invention is directed to a dry, flowable and compressible composition, useful as a pharmaceutical excipient, which composition comprises a mixture of hydrophobic and hydrophilic poly(ethylene oxide)-polypropylene oxide)-poly(ethylene oxide) block copolymers, and which possesses a Carr index of less than about 20. In other aspects, the present invention is directed a pharmaceutical composition comprising such adjuvant and a pharmaceutically active ingredient; as well as to a method of making the compositions.

Abstract: The present invention is a method for treating non-small cell lung cancer in a subject in need thereof, comprising administering to the subject an effective amount of a bis(thiohydrazideamide) compound of formula (I): wherein the variables are defined herein. Furthermore, pharmaceutical compositions, combination therapies, and uses thereof are also provided in the present application.

Abstract: A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1?, 2? or 3?-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: Conformationally locked 2?,4?-carbocylic nucleosides with improved thermal and nuclease stability are disclosed. Oligonucleotides incorporating the locked nucleosides, and methods of treating disease states, are also disclosed.

Abstract: Oligonucleotide analogues are provided that incorporate 5-aza-cytosine in the oligonucleotide sequence, e.g., in the form of 5-aza-2?-deoxycytidine (decitabine) or 5-aza-cytidine. In particular, oligonucleotide analogues rich in decitabine-deoxyguanosine islets (DpG and GpD) are provided to target the CpG islets in the human genome, especially in the promoter regions of genes susceptible to aberrant hypermethylation. Such analogues can be used for modulation of DNA methylation, such as effective inhibition of methylation of cytosine at the C-5 position. Methods for synthesizing these oligonucleotide analogues and for modulating nucleic acid methylation are provided. Also provided are phosphoramidite building blocks for synthesizing the oligonucleotide analogues, methods for synthesizing, formulating and administering these compounds or compositions to treat conditions, such as cancer and hematological disorders.

Abstract: The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound. In particular, the method relates to a methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional anti-neoplastic compound.

Abstract: The present invention provides organic arsenicals. Many of these compounds have potent in vitro cytotoxic activity against numerous human tumor cell lines, both of solid and hematological origin, as well as against malignant blood cells from patients with leukemia.

Abstract: Provided herein are methods of treating a proliferative disease in a subject, comprising administering to the subject a therapeutically effective amount of AC220 and a nucleoside analog, a topoisomerase inhibitor or an anthracycline, or a combination thereof.

Abstract: There are provided, inter alia, lipophilic monophosphorylated derivatives of gemcitabine. There are further provided nanoparticles compositions incorporating lipophilic monophosphorylated derivatives of gemcitabine, pharmaceutical compositions thereof, and a method of treating cancer or a viral infection in a subject in need thereof, which method includes administration of a pharmaceutical composition disclosed herein.

Abstract: The invention relates to compositions and methods for treating cancer comprising administering to a subject in need a pharmaceutically effective dose of a cancer stem cell inhibitor, methods of inhibiting the growth of cancer stem cells or tumor initiating cell comprising administering to a subject in need a pharmaceutically effective dose of a cancer stem cell inhibitor, and methods of enhancing the biological effects of chemotherapeutic drugs or irradiation on cancer cells comprising administering to a subject in need a pharmaceutically effective dose of a chemotherapeutic drug and a pharmaceutically effective dose of a cancer stem cell inhibitor.

Abstract: A combination therapy is disclosed for treating cancer. The method comprises administering to a cancer patient a therapeutically effective amount of trans-[tetrachlorobis(1H-indazole)ruthenate(III)] or a pharmaceutically acceptable salt thereof, and administering to the patient a therapeutically effective amount of one or more other anti-cancer agents as disclosed herein.

Abstract: The present invention provides a therapeutic combination comprising (a) a compound of formula (I) as set forth in the specification and (b) one or more antineoplastic agents selected from the group consisting of an alkylating or alkylating-like agent, an antimetabolite agent, a topoisomerase I inhibitor, a topoisomerase II inhibitor, an antimitotic agent and radiation wherein the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate thereof.

Abstract: A composition comprising (a) one or more ?-3 fatty acids selected from DHA, DPA and EPA, (b) uridine or its equivalent, and (c) a methyl donor, useful in the treatment of a person having characteristics of a prodromal dementia patient. The characteristics include e.g. a level of more than 350 ng Total-tau per liter cerebrospinal fluid (CSF), and a weight ratio of abeta-42/Phospho-tau-181 of less than 6.5 in CSF.

Abstract: A pharmaceutical solution suitable for oral administration comprising ?-L-thymidine/2?-deoxy-L-thymidine (telbivudine), a pharmaceutically suitable solvent system, one or more taste-enhancing/masking agents, a preservative system, and a buffer system suitable to allow both drug stability and preservation.

Abstract: A novel network of tumorigenic prognostic factors is identified that plays a critical role in advanced pancreatic cancer (PC) pathogenesis. This interactome is interconnected through a central tumor suppressive microRNA, miR-198, which is able to both directly and indirectly modulate expression of the various members of this network to alter the molecular makeup of pancreatic tumors. When this tumor signature network is intact, miR-198 expression is reduced and patient survival is dismal; patients with higher miR-198 present an altered tumor signature network, better prognosis and increased survival. Further, MiR-198 replacement reverses tumorigenicity in vitro and in vivo. embodiment of the disclosure is a method of treating cancer in an individual, comprising the step of increasing the level of active microRNA-198 molecules in the pancreatic cancer tumor cells of the individual by an amount sufficient to cause an improvement in the pancreatic cancer in the individual.

Abstract: What is disclosed in the invention is a preparation method of a supercritical Cinnamomum subavenium extract, which is made from the material, the dried stem of C. subavenium. The extract is obtained by extracting C. subavenium which is pulverized as particles with supercritical carbon dioxide fluid. The C. subavenium extract or its active ingredient, subamolide A, can be used to inhibit the growth of human urothelial carcinoma cell lines. In addition, the C. subavenium extract (or subamolide A) is able to synergistically inhibit the growth of human urothelial carcinoma cell lines with cisplatin (CDDP) or gemcitabine (Gem). Therefore, the C. subavenium extract (or subamolide A) can be an anticancer drug alone, or forms a pharmaceutical composition with CDDP (or Gem) to treat with cancers in respect of urinary system.

Abstract: The present teachings include ratiometric combinatorial drug delivery including nanoparticles, multi-drug conjugates, pharmaceutical compositions, methods of producing such compositions and methods of using such compositions, including in the treatment of diseases and conditions using drug combinations.

Abstract: The subject invention relates to determining the presence and level of hENT1 expression in tumor tissue that is appropriate for gemcitabine therapy, and more importantly, the level of hENT1 expression that signifies that treatment with a gemcitabine derivative is a more appropriate strategy.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

Abstract: Polymeric nanoparticles with a hydrophobic core and a hydrophilic shell are formed from: 1) N-isopropylacrylamide (NIPAAM), at a molar ratio of about 50% to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral; either water-soluble vinyl derivatives like vinylpryolidone (VP) or vinyl acetate (VA), or water insoluble vinyl derivaties like methyl methacrylate (MMA) or styrene (ST), at a molar ratio of about 10% to about 30%; and acrylic acid (AA), at a molar ration of about 10% to about 30%.

Abstract: A pharmaceutical composition or combination drug, which contains, as active ingredients, (a) a coordination compound composed of a block copolymer represented by the following formula I or formula II and cisplatin, and (b) gemcitabine hydrochloride. In the formulae I and II, R1, A, R2, R3, m and n are as defined in the description.

Abstract: The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula:

Abstract: The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula:

Abstract: Methods of treating, preventing or managing antecedent hematologic disorders, such as myelodysplastic syndrome, including chronic myelomonocytic leukemia are disclosed. The methods encompass the administration of SNS-595. Also provided are methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. In certain embodiments, the method of treatment comprise administering SNS-595 in combination with cytarabine. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods are also disclosed.

Abstract: The present invention features interferon- and ribavirin-free therapies for the treatment of HCV. Preferably, the treatment is over a shorter duration of treatment, such as no more than 12 weeks. In one aspect, the therapies comprise administering at least two direct acting antiviral agents without interferon and ribavirin to a subject with HCV infection. For example, the therapies comprise administering to a subject an effective amounts of therapeutic agent 1, therapeutic agent 2 (or therapeutic agent 3), and an inhibitor of cytochrome P450 (e.g., ritonavir).

Abstract: The present invention features interferon- and ribavirin-free therapies for the treatment of HCV. Preferably, the treatment is over a shorter duration of treatment, such as no more than 12 weeks. In one aspect, the therapies comprise administering at least two direct acting antiviral agents without interferon and ribavirin to a subject with HCV infection. For example, the therapies comprise administering to a subject an effective amounts of therapeutic agent 1, therapeutic agent 2 (or therapeutic agent 3), and an inhibitor of cytochrome P450 (e.g., ritonavir).

Abstract: The present invention relates to a method of treating pancreatic cancer in a subject in need thereof by administering an effective amount of a composition containing (A) tegafur and (B) gimeracil in conjunction with radiotherapy.

Abstract: Methods and systems for identifying and treating a patient suspected of having a tumor susceptible to growth inhibition by anti-progestins are provided. The degree of focal distribution of the progesterone receptor can be used to identify tumors susceptible to treatment with anti-progestin therapy.

Abstract: A compound for use in the treatment or prophylaxis of viral infections such, for example as chicken pox or shingles caused by the Varicella Zoster virus, said compound having the general formula (II): wherein X is O, S, NH or CH2, Y is O, S or NH, Z is O, S or CH2, R1 is C1-6 alkyl, preferably n-alkyl, e.g., n-pentyl or n-hexyl, and one of R2 and R3 is OH, and the other of R3 and R2 is a neutral, non-polar amino acid moiety, or a pharmaceutically acceptable salt or hydrate thereof. Said neutral, non-polar amino acid moiety R2 or R3 may be (IV): in which R4, R5, R6 and R7 are each independently H or C1-2 alkyl. In preferred embodiments, one of R2 or R3 is valine, leucine, isoleucine or alanine, particularly valine.

Abstract: A controlled release delivery composition comprising: a housing adapted for oral administration; and a plurality of discrete vehicles assembled within the housing, each of the vehicles are not compressed together, each of the vehicles being a bead, a pellet, a tablet, and/or granules compressed into a preselect shape, wherein each of the vehicles comprise a different combination and/or amount of an active agent, an amino acid, a buffer, and a polymer, such that each of the vehicles comprises a different active agent and/or release property from each other, wherein each of the vehicles releases the active agent independently of each other, and wherein each of the vehicles remains independent from each other and intact within the housing prior to oral administration of the delivery composition.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

Abstract: This invention relates to novel 2-{6-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-2-methyl-pyrimidin-4-ylamino}-thiazole-5-carboxylic acid (2-chloro-6-methyl-phenyl)-amide derivatives, and pharmaceutically acceptable acid addition salts thereof. The invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by the inhibition of kinases including Src-kinase and Bcr-Abl kinase.

Abstract: The present application refers to methods for cancer diagnosis and treatment, particularly in types of cancers associated with aberrant CpG methylation of the miR-34a promoter.

Abstract: This invention relates to methods and compositions for treating pancreatic cancer. More specifically, this invention relates to treating pancreatic cancer with certain ATR inhibitors in combination with gemcitabine and/or radiation therapy. This invention also relates to methods and compositions for treating non-small cell lung cancer. More specifically, this invention relates to treating non-small cell lung cancer with an ATR inhibitor in combination with cisplatin or carboplatin, etoposide, and ionizing radiation.

Abstract: The present invention relates to the treatment and/or prevention of aortic valve stenosis (AVS) and valve mineralization. Particularly, the invention provides a target for intervention in the treatment or prevention of AVS through the administration of the P2Y2 receptor agonists. Also, the invention provides means to treat hypertension related to decreased arterial compliance and vascular calcification.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein. Additionally, the present invention also relates to novel processes for the production of various morpoholine based intermediates.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; solid forms of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I-1: wherein the variables are as defined herein. Additionally, the compounds of this invention have formula II: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

Abstract: A method and composition for treating a host infected with a Caliciviridae virus, such as a Norovirus, comprising administering an effective treatment amount of a described modified nucleoside or a pharmaceutically acceptable salt thereof, is provided.

Abstract: The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2?R)-2?-deoxy-2?-fluoro-2?-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: Provided herein are methods for the diagnosis and treatment of human melanoma and prediction of early disease genesis to metastasis by assessing CpG island methylation or expression level of epigenetically regulated differentially expressed coding or non-coding genes. Methods of treatment of human melanoma by modifying or regulating the same pathways are also provided.

Abstract: The invention provides combination therapy, wherein one or more other therapeutic agents are administered with indibulin or a pharmaceutically acceptable salt thereof and the combination is synergistic. Another aspect of the invention relates to the treatment of cancer with indibulin as a single agent. Another aspect of the invention relates to dosing regimen for administration of oral dosage forms of indibulin.

Abstract: This application relates to combination therapies including triciribine compounds and epidermal growth factor receptor inhibitor compounds, particularly erlotinib-like compounds and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation.

Abstract: Disclosed are Mannich base N-oxides of drugs containing acidic N—H groups. Pharmaceutical compositions comprising a therapeutically effective amount of Mannich base N-oxides, or a N-oxide rearrangement product, pharmaceutically acceptable salt or prodrug thereof, are also disclosed. Further, disclosed are methods of using the compounds, alone or in combination with one or more other active agents or treatments.

Abstract: The invention relates to phosphorylation inhibitor compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating cell proliferative disorders, especially cancer.

Abstract: Among other things, the present disclosure provides a method including the steps of: obtaining a uterine sample; and detecting and/or characterizing in the uterine sample an ovarian cancer biomarker (e.g., CA125).

Abstract: The present invention relates to 2?-chloroacetylenyl-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related ?-D and ?-L-nucleoside derivatives.

Abstract: The present invention provides compositions methods for treating susceptible viral infections, especially hepatitis C viral (HCV) infections as well as co infections of HCV with other viruses such as HBV and/or HIV. In one embodiment, the present invention provides compositions having the formula (I) and their use in treating viral infections: or a pharmaceutically acceptable salt, ester, stereoisomer, tautomers, solvate, prodrug, or combination thereof.