Abstract: Disclosed is a steviol glycoside referred to as rebaudioside D3. Rebaudioside D3 has five ?-D-glucosyl units connected to the aglycone steviol. Also disclosed are methods for producing rebaudioside D3, a UDP-glycosyltransferase fusion enzyme, and methods for producing rebaudioside D and rebaudioside E.

Abstract: The invention relates to a method for the treatment of triple negative breast cancer in a subject, comprising administering to the subject an effective amount of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide, or a pharmaceutically acceptable salt thereof, and an effective amount of carboplatin, in combination with standard of care.

Abstract: Embodiments of the present invention include methods and compositions for ameliorating cancer. Some embodiments include methods and compositions for ameliorating pancreatic cancer targeting the CXCR4 receptor and the CXCL12 ligand.

Abstract: A method for reducing arrhythmic risk associated with cardiomyopathy includes administering a composition containing NAD+ or a mitochondrial targeted antioxidant to an individual in need thereof.

Abstract: A method for reducing arrhythmic risk associated with cardiomyopathy by improving conduction velocity, includes administering a composition containing NAD+ or a mitochondrial targeted antioxidant to an individual or person in need thereof.

Abstract: Methods of treating cancer comprising administering inhibitors of glucose transporters (GLUTs) are provided. Methods of predicting whether a cancer will respond to treatment with a GLUT inhibitor also are provided.

Abstract: The present invention relates in general to the field of targeted drug delivery of anti-cancer drugs. More precisely, the present invention concerns polymer drug conjugates, namely, conjugates of poly(organo)phosphazenes and anti-cancer drugs, wherein the conjugates are suitable to selectively release anti-cancer drugs in tumor tissue. In addition, the present invention relates to a method for manufacturing such poly(organo)phosphazene molecule conjugates, to poly(organo)phosphazene molecule conjugates for use in medicine, in particular, to poly(organo)phosphazene molecule conjugates for use in the treatment of cancer, and to pharmaceutical compositions comprising such poly(organo)phosphazene molecule conjugates.

Abstract: Linkers for binding drugs to cell binding agents are modified to hydrophilic linkers by incorporating a polyethylene glycol spacer. The potency or the efficacy of the cell-binding agent-drug conjugates is surprisingly enhanced several folds in a variety of cancer cell types, including those expressing a low number of antigens on the cell surface or cancer cells that are resistant to treatment. A method for preparing maytansinoids bearing a thioether moiety and a reactive group which allows the maytansinoid to be linked to a cell-binding agent in essentially a single step is also provided.

Abstract: The present invention provides an aminopyrazole compound, or a pharmaceutically acceptable salt thereof, that inhibits Chk1 and is useful in the treatment of cancer.

Abstract: The present invention provides a novel system and method for sulphur and metal removal from crude oil and all liquid fuel fractions to biofuels by means of ultrasonic cavitation to enhance chemical reactions of said contaminants with sodium or potassium methylate and a water/fluoride mix in separate stages obtaining a solid form which is filtered out by the use of a centrifuge system. The resulting fuel is molecularly stable and cleaner than regular fuels.

Abstract: The present invention is directed to methods of prognosing relapsed leukemia in a subject. These methods are based on the detection of one or more relapse-specific gene mutations in a patient sample. The present invention further relates to methods of preventing and treating relapse leukemia in a subject based on the determined prognosis of the subject.

Abstract: Provided are methods of using curcuphenol compounds to increase expression of major histocompatibility complex class I (MHC-I) antigen in cells, particularly on the surface of diseased cells such as cancer cells, and thereby increase the immunogenicity of the cells. Also provided are pharmaceutical compositions that comprise curcuphenol compounds and methods of use thereof, for instance, to treat various cancers, alone or in combination with other therapies.

Abstract: The present invention relates to inhibitors of the activity of Complex (III) of the mitochondrial electron transport chain and use thereof in treatment and/or prevention of cancers presenting tumour-initiating cells. The present invention further relates to pharmaceutical compositions containing said inhibitors alone or in combination with other pharmaceutically active agents, and their use as medicaments or as agrochemicals where their properties as inhibitors of the mitochondrial respiration is of benefit.

Abstract: The present invention relates to the BAD pathway's influence on development, progression, chemo-sensitivity, and overall survival for multiple human cancers and its potential as a therapeutic target to increase chemo-sensitivity. BAD pathway expression was associated with the development and/or progression of breast, colon, and endometrial cancers, relapse-free survival from breast cancer, and overall survival from ovarian, colon, and brain cancers. Expression was also associated with in vitro sensitivity to a range of cytotoxic agents. pBAD levels were higher in cancer versus immortalized normal cells and chemo-resistant versus—sensitive cancer cells and associated with increased cell proliferation.

Abstract: Controlled release dosage formulations for the delivery of one or more HIF-1 inhibitors are provided. The controlled release formulations contain one or more HIF-1 inhibitors conjugated to or dispersed in a polymeric vehicle. The one or more HIF-1 inhibitors can be dispersed or encapsulated in a polymeric matrix. In some embodiments, the one or more HIF-1 inhibitors are covalently bound to a polymer, forming a polymer-drug conjugate. Polymeric vehicles can be formed into implants, microparticles, nanoparticles, or combinations thereof. Controlled release HIF-1 formulations provide prolonged therapeutic benefit while lowering side effects by releasing low levels of one or more HIF-1 inhibitors and/or HIF-1 inhibitor conjugates over a prolonged period of time. Controlled release dosage formulations can be used to treat or prevent a disease or disorder in a patient associated with vascularization, including cancer, obesity, and ocular diseases such as wet AMD.

Abstract: Drug delivery compositions are disclosed that include multimolecular assemblies that have heparosan polymer(s) attached thereto and therapeutic(s) (and/or potential therapeutic(s)) entrapped, carried, or otherwise bound in the multimolecular assemblies. Methods for producing and using the drug delivery compositions are also disclosed.

Abstract: Synergistic cancer therapy drug combinations include therapeutically effective amounts of at least one chemotherapeutic drug or agent with a fortified decoction dosage form comprising from about 10 mg to about 6,000 mg each of ?-sitosterol, isovanillin, and linolenic acid. The decoction dosage preferably includes plant extract(s) of the genus Arum fortified with effective amounts of ?-sitosterol, isovanillin, and linolenic acid not derived from the plant. The combination may be in various forms including aqueous dispersions, gels, ampules, powders, capsules, pills, or tablets, and are normally administered orally to patients. The anticancer combinations have therapeutic effects on cancerous tissue which are greater than the sum of the individual therapeutic effects of the fortified decoction dosage form and the at least one chemotherapeutic agent on the cancerous tissue.

Abstract: Materials and methods are provided for producing and using aptamers useful as oncology therapeutics capable of binding to PDGF, PDGF isoforms, PDGF receptor, VEGF, and VEGF receptor or any combination thereof with great affinity and specificity. The compositions of the present invention are particularly useful in solid tumor therapy and can be used one or in combination with known cytotoxic agents for the treatment of solid tumors. Also disclosed are aptarmers having one or more CpG motifs embedded therein or appended thereto.

Abstract: The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Abstract: The present invention includes drug-loaded, polymer nanoparticles and liposomes further incorporating a non-paramagnetic, bioorganic CEST agent. The CEST agent allows for an alternative approach to accomplish MR-compatible in vivo tracking of drug-loaded polymer nanoparticles and liposomes, including simultaneous multi-color mapping of more than one particle type, or of the same particle type delivered via two different routes (e.g., systemic versus local). Additionally, the present invention can include a library of biodegradable diamagnetic (DIA)CEST agents. These DIACEST agents can be incorporated into nanoparticle-based delivery systems, such as stealth liposomes loaded with doxorubicin and stealth polymer nanoparticles loaded with paclitaxel. These systems can be tracked, according to an embodiment of the present invention using CEST-based MRI (compared to SPECT/CT) as a method to monitor the efficiency with which the nanoparticles reach the targeted tumors and how long they persist.

Abstract: Synthesis and characterization of starch based pH-responsive nanoparticles for controlled drug delivery are described. Polymethacrylic acid grafted starch (PMAA-g-St) nanoparticles with various molar ratio of starch to MAA were synthesized by a new one-pot method that enabled simultaneous grafting of PMAA and nanoparticle formation in an aqueous medium. NMR data showed that polysorbate 80 was polymerized into the graft polymer. Nanoparticles were relatively spherical with narrow size distribution and porous surface morphology and exhibited pH-dependent swelling in physiological pH range. The particle size and magnitude of volume phase transition were dependent on PMAA content and formulation parameters such as surfactant levels, cross-linker amount, and total monomer concentration. The results showed that the new pH-responsive nanoparticles possessed useful properties for controlled drug delivery.

Abstract: The present invention provides sorafenib analogs for use in a method of treating a disease mediated by p21, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I. The present invention also provides methods of inhibiting p21 in a cell comprising contacting the cell with an effective amount of a compound of formula I.

Abstract: The present invention relates to compounds and pharmaceutical compositions for treating cellular proliferative disorders, e.g., in patients having one or more p53-deficient cells, screening assays for identifying such compounds, and methods for treating such disorders.

Abstract: The disclosure provides a biomedical composition, including: a hyaluronic acid; a modified histidine; and a polymer or C4-C20 alkane, wherein the modified histidine and the polymer or C4-C20 alkane are grafted to at least one primary hydroxyl group of the hyaluronic acid to allow the hyaluronic acid to form a hyaluronic acid derivative, wherein a graft ratio of the modified histidine is about 1-100%, and a graft ratio of the polymer or C4-C20 alkane is about 0-40%.

Abstract: The application describes a method of screening for breast cancer by testing fro the amount of HAGE (Helicase antigen) in a sample of breast tissue. Methods of prognosis of samples of breast cancer tumours are also provided. HAGE+ ER? (estrogen receptor-) cancers are indicated as being amenable to chemotherapy. Methods of treating breast cancers with HAGE-specific CTA antigen or HAGE-specific antibodies are also provided.

Abstract: This disclosure provides a method for determining if a patient is likely to, or not likely to, experience ovarian cancer utilizing SP17 as a biomarker. It also provides methods and therapies to treat patients identified as at risk for ovarian cancer or alternatively, as identified as having a poorer prognosis.

Abstract: The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Abstract: The present invention relates to substituted imidazopyridazine compounds of general formula I in which R3, R5 and A are as defined in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

Abstract: A method for treating a leukemia patient that is resistant to a thymidine kinase inhibitor (TKI) other than imantinib comprising administering a cephalotaxine to said patient until said patient demonstrates a hematological or cytological response to said leukemia.

Abstract: Nanocells allow the sequential delivery of two different therapeutic agents with different modes of action or different pharmacokinetics. A nanocell is formed by encapsulating a nanocore with a first agent inside a lipid vesicle containing a second agent. The agent in the outer lipid compartment is released first and may exert its effect before the agent in the nanocore is released. The nanocell delivery system may be formulated in pharmaceutical composition for delivery to patients suffering from diseases such as cancer, inflammatory diseases such as asthma, autoimmune diseases such as rheumatoid arthritis, infectious diseases, and neurological diseases such as epilepsy. In treating cancer, a traditional antineoplastic agent is contained in the outer lipid vesicle of the nanocell, and an antiangiogenic agent is loaded into the nanocore. This arrangement allows the antineoplastic agent to be released first and delivered to the tumor before the tumor's blood supply is cut off by the antianiogenic agent.

Abstract: The present invention relates to a novel composition useful in targeted diagnostic and/or therapy of a target site, such as cancerous tissue. The composition and methods disclosed herein find particular use in diagnosing and imaging cancerous tissue. The present invention provides a new diagnostic tool for the utilization of positron emission tomography (PET) imaging technique.

Abstract: The invention relates to a combination comprising the N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)-ethyl]-amino]methyl]phenyl]-2E-2-propenamide; and one or more pharmaceutically active agents; pharmaceutical compositions comprising said combination; methods of treatment comprising said combination; processes for making said combination; and a commercial package comprising said combination.

Abstract: The present invention relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, intermediates thereto, and uses thereof. QS-7 is a potent immuno-adjuvant that is significantly less toxic than QS-21, a related saponin that is currently the favored adjuvant in anticancer and antiviral vaccines. Tedious isolation and purification protocols have hindered the clinical development of QS-7. A novel semi-synthetic method is provided wherein a hydrolyzed prosapogenin mixture is used to synthesize QS-7, QS-21, and related analogs, greatly facilitating access to QS-7 and QS-21 analogs for preclinical and clinical evaluation.

Abstract: Mucus-penetrating liposomal nanoparticles and methods of making and using thereof are described herein. The nanoparticles contain one or more lipids, one or more PEG-conjugated lipids, and optionally one or more additional materials that physically and/or chemically stabilize the particles. The nanoparticle have an average diameter of about 100 nm to about 300 nm, preferably from about 100 nm to about 250 nm, more preferably from about 100 nm to about 200 nm. The particles are mobile in mucus. The liposomes can further contain one or more therapeutic, prophylactic, and/or diagnostic agent to be delivered to a mucosal surface, such as the CV tract, the colon, the nose, the lungs, and/or the eyes. The liposomes can further contain one or more CEST agents to allow real time imaging of the particles in a live animal. The particles may also further contain an imaging agent, such as a fluorescent label.

Abstract: The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as CDM-Hs, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by introducing cytotoxic moieties to gp120-expressing cells, thereby causing cell death and preventing cell infection and spread of HIV. It is shown that CDM-Hs bind to gp120 and gp-120 expressing cells competitively with CD4, and these compounds cause cell death of HIV-infected cells, thereby decreasing viral infectivity. Compounds and methods are described herein.

Abstract: A porous polymeric matrix and a device for optically-controlled release of chemicals allow a controlled and localized administration of a chemical species, by exploiting the thermosensitivity of amphiphilic supramolecular structures used as reservoir without this requesting a direct heating, at the same time by guaranteeing a precise dosage and positioning of the release of the chemical species.

Abstract: Disclosed are compositions and methods for treating anthrax, inhibiting anthrax toxins and inhibiting anthrax toxin-induced cytotoxicity. Carboxylic acid-containing small molecules can be used in the methods and compositions disclosed herein, for example, sulindac and derivatives thereof may be used. Methods of screening for carboxylic acid-containing small molecules that can be used to treat anthrax are disclosed. Targeting the anthrax toxin reduces the risks of anthrax spores.

Abstract: Provided herein are compositions comprising oligomeric compounds. In certain embodiments, the oligomeric compounds are useful as miRNA mimics. The oligomeric compounds may mimic the activity of miR-34. Also provided herein are methods for the treatment of cancer.

Abstract: The present invention relates to a class of hydroxamic acid compounds of Formula (I), which act as alkylating agents and/or inhibitors of the HDAC pathway, having potential utility in the treatment of a neoplastic disease and immune diseases.

Abstract: The present application relates to compositions comprising and methods of using a liposome comprising a pHLIP polypeptide, wherein a lipid bilayer of the liposome is substantially free of the pHLIP polypeptide.

Abstract: The present invention relates to compounds and compositions and their application as pharmaceuticals for treating, preventing, or reversing injury to skeletal or cardiac muscles, for treating or preventing diseases relating to the structure and function of skeletal or cardiac muscle, and for inducing regeneration or restructuring of skeletal or cardiac muscle as a means of treating diseases relating to abnormalities in skeletal or cardiac muscle structure and function in a human or animal subject.

Abstract: In one embodiment, the present application discloses synthetic LDL nanoparticles comprising mixtures of components selected from the group consisting of phospholipids, triglycerides, cholesterol ester and free cholesterol; optionally further comprising an agent selected from the group consisting of natural antioxidants, ubiquinol and vitamin E, and methods for preparing the synthetic nanoparticles. The disclosed synthetic LDL nanoparticles are capable of selectively delivering lipophilic drugs and prodrugs to cellular targets expressing LDL receptors after intra venous injection.

Abstract: The present invention relates to methods of treating pulmonary hypertension in a subject including administering to the subject a therapeutically effective dose of at least one anthracycline.

Abstract: A process for the preparation of nanoparticles from polysaccharides and derivatives thereof, by their specific partial oxidation to produce aldehyde groups and attachment of compounds with amino or other group with the R—NH2 bond which react with aldehyde groups, and a nanoparticle produced by such process.

Abstract: The invention relates to compositions of DOTA derivative compounds, lanthanoid-DOTA derivative molecular complex, and lanthanoid-complex encapsulated solid lipid particles or capsules, and methods of making and using the compositions. The solid lipid particles or capsules contain micelle cores stabilized by a hyperbranched polymer shell based from a crosslinked DOTA derivative compound or crosslinked lanthanoid-DOTA derivative complex. These solid lipid particles or capsules can be used in various applications, such as contrast agents or drug delivery vehicles.

Abstract: Methods and compositions containing a phorbol ester or a derivative of a phorbol ester are provided for the treatment of chronic and acute conditions. Such conditions may be caused by disease, be symptoms or sequelae of disease. Chronic and acute conditions may be due to viral infections such as HIV and AIDS, neoplastic diseases stroke, kidney disease, urinary incontinence, autoimmune disorders, Parkinson's disease, prostate hypertrophy, aging, or the treatment of such diseases. Additional compositions and methods are provided which employ a phorbol ester or derivative compound in combination with at least one additional agent to yield more effective treatment tools against acute and chronic conditions in mammalian subjects.

Abstract: This disclosure describes methods of screening for compounds that disrupt the interaction between DNMT1 and the gamma-globin promoter or between LSD-1 and the gamma-globin promoter. This disclosure describes methods of screening for compounds that de-repress the gamma-globin gene.

Abstract: The invention relates to the treatment of cancer using DNA damaging agents. The invention provides methods for treating a mammal with cancer, the method comprising inhibiting in the mammal acidic residue methyltransferase (Arm1) in combination with administering to the mammal a DNA damaging agent. The invention further provides pharmaceutical formulations comprising an inhibitor of acidic residue methyltransferase (Arm1) and a DNA damaging agent.

Abstract: Reductively degradable micelles comprising poly(-?amino ester)s-g-poly(ethylene glycol) amphiphilic copolymers provided with aromatic phenylbutylamine side groups, suitable for sequestering therein anthrocyclines. The anthrocycline-loaded reductively degradable micelles are useful for therapeutic treatment of cancers.

Abstract: A novel compound, (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one, is provided herein. (E)-1-(pyridyn-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)-prop-2-en-1-one is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) with surprisingly superior efficacy and pharmacodynamic properties in vitro and in vivo. Also provided are pharmaceutical compositions including the compound and methods of use of the compound in treating cancer and tumors in vivo, as well as inhibiting glycolytic flux and PFKFB3 enzymatic activity in cells.