Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal. Methods for modifying the genome of non-nuclear organelles are also provided.

Abstract: Agents that reduce the amount of IGFBP-2 and/or IGFBP-5 and that are known to be useful in the treatment of cancer result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. In overcoming this, the present invention provides a combination of therapeutic agents that is useful in the treatment of cancer. The combination includes an agent that reduces the amount of IGFBP-2 and/or IGFBP-5 and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells. In some embodiments of the invention, the agent that reduces IGFBP-2 and/or IGFBP-5 is a bispecific antisense species. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.

Abstract: The invention provides methods and compositions for modulating the HGF/c-met signaling pathway, in particular by inhibiting a hyperstabilized c-met protein.

Abstract: Hemofiltration systems and methods to treat an Inflammatory Mediator Related Disease in a patients, including chronic and acute diseases, may include a hemofilter and an adsorptive device. The systems and methods may further include one or more therapeutic agents administered to the patient. The hemofilter removes ultrafiltrate from a blood stream extracted from the patient to create a filtered blood stream and an ultrafiltrate stream. The adsorptive device may include one or more adsorbent materials and may be used to adsorb inflammatory mediators from the ultrafiltrate stream received from the hemofilter to create a post adsorption ultrafiltrate stream. The post adsorption ultrafiltrate stream may be selectively combined with the filtered blood stream and together with the filtered blood stream may be returned to the mammal. Other systems and methods are disclosed.

Abstract: The invention relates to methods and compounds for treating or preventing cancer. Methods for treating or preventing cancer, for inhibiting tumor growth, reducing tumor volume, inhibiting tumor progression, inhibiting metastasis, and improving survival are provided herein.

Abstract: The invention is directed to a method for preventing nasolacrimal duct obstruction (NLDO) in a patient receiving high dose radioactive iodine for treatment of cancer. The method includes administering an effective amount of perchlorate anion to the eyes of the patient.

Abstract: The present invention relates to methods for the treatment, the prognosis and the diagnosis of non-small cell lung cancer.

Abstract: The invention relates to novel polyalkylene glycol compounds and methods of using them. In particular, compounds comprising a novel polyethylene glycol conjugate are used alone, or in combination with antiviral agents to treat a viral infection, such as chronic hepatitis C.

Abstract: In general, the present invention provides methods for treating disorders associated with the amygdala. The methods of treatment are based on the administration of a therapeutically effective amount of secretin to an individual suffering from a disorder associated with the amygdala, e.g., bipolar disorder or a substance use disorder.

Abstract: The present invention relates to the field of diagnosis and therapy of hematological malignancies based on the tumor antigen FMR1NB (also called NY-SAR-35, Cancer/testis antigen 37 or Fragile X mental retardation 1 neighbor protein) and agents specifically targeting this antigen or cells expressing the same, e.g., antibodies. The inventors were able to prove that the molecule is expressed on the cell surface and thus represents a particularly advantageous target in cancer therapy and vaccination. Surprisingly, FMR1NB was found to be associated with hematological malignancies, e.g. acute myeloid leukemia (AML) or chronic myeloid leukemia (CML).

Abstract: Numerous diseases have been linked to the production of regulator cells. The present invention relates to the observation that the immune system is cycling in these diseases. Based on these observations, the present invention provides methods for treating diseases such as cancer and a HIV infection. The present invention also relates to methods of determining when a therapy to treat a disease characterized by the production of regulator cells should be administered to a patient.

Abstract: The placing of a drug that is suitable for parenteral administration on bubbles formed with sterile gases produces an exponential increase in its active surface area with a decrease in the diameter of the bubble, modifies the kinetics of its distribution and, thanks to its micronization, increases its therapeutic effect. Furthermore, the echogenicity of the bubbles allows us to follow them on ultrasound after their injection, so that we can visualise the medicament and, thanks to its steerability, can direct it to the selected site or prevent it from reaching undesired areas. This pharmaceutical form is of interest in the treatment of diseases that require a greater local action of the injected drugs than can be achieved with the pharmaceutical forms in current use.

Abstract: The invention provides methods of preventing or treating a condition associated with DNA damage in an animal comprising the administration of a substance that interferes with the activity of the CUL4A ubiquitin ligase. The invention also provides a substance that interferes with the activity of CUL4A, as well as compositions comprising the interfering substance and a carrier. The substance of the invention preferably enhances nucleotide excision repair activity in an animal. The invention further provides methods of identifying substances that negatively or positively modulate the expression and/or activity of CUL4A.

Abstract: The present disclosure describes the broadly active chelation of diverse divalent 2+ metal cations by any oligonucleotide (ON), regardless of size or modification. This chelation effect is specific to cations which are divalent (or of higher valency) and results in the formation of oligonucleotide chelate complexes which do not behave like salts. It is described herein a novel composition of an ON chelate complex prepared using any ON and a divalent metal cation and methods for the suppression of anti-coagulation and or subcutaneous injection site reactions and or improved tolerability with oligonucleotides by the use of ON chelate complexes during oligonucleotide administration.

Abstract: The present invention relates generally to dental diseases, caries and periodontal disease. More specifically, the invention relates to Lactoferrin and Statherin fusion proteins (STAT-LF) along with therapeutic, diagnostic and research uses for these polypeptides. The present invention also provides methods of treating dental diseases, caries and periodontal disease.

Abstract: A novel dosing regimen for the administration of botulinum toxin based on the pattern, quantity, and location of neuromuscular junctions in the target tissue. Because the number of neuromuscular junctions in a target tissue remains generally stable throughout life and because the pharmacological effect of botulinum toxin is localized at the neuromuscular junction, dosing efficacy is unaffected by muscle mass, age of the patient, or body weight.

Abstract: This invention provides methods for identifying genes associated with cognitive impairment and for identifying compounds useful in the treatment of cognitive impairment. The methods can in particular be used to identify genes associated with, and compounds useful in treating, cognitive impairment in aging.

Abstract: According to some embodiments, the present invention provides compositions and methods for making and using multifunctional polymerized liposomes finding relevant application in medical sciences, particularly in bioimaging, diagnostics, drug delivery, and drug formulation. The compositions and methods involve lipids that are both polymerizable and have a “clickable” group that provides the ability to functionalize via a click reaction with various functional moieties useful for the above-listed applications.

Abstract: The present invention relates to a composition for inducing embryonic stem cell differentiation comprising a MEK/ERK (mitogen-activated protein kinase kinase/extracellular regulated kinase) signal transduction inhibitor and BMP (bone morphogenetic protein), and a method for inducing differentiation of embryonic stem cells into mesodermal cells using the same. Further, the mesodermal cells obtained by the above method are able to differentiate into various mesenchymal tissue cells. In particular, the present invention relates to a method for inducing differentiation into hemangioblast by culturing the mesodermal cells obtained by the above method in the presence of VEGF (vascular endothelial cell growth factor) and bFGF (basic fibroblast growth factor). The differentiated hemangioblasts can be further differentiated into vascular endothelial cells, vascular smooth muscle cells, and hematopoietic stem cells under various culture conditions.

Abstract: IGF1R biomarkers useful in a method for identifying and monitoring a mammal that will respond therapeutically to a method of treating cancer comprising administering an IGF1R modulator, wherein the method comprises (a) exposing the mammal to the IGF1R modulator and (b) measuring in the mammal the level of the at least one biomarker, wherein a difference in the level of the at least one biomarker measured in (b) compared to the level of the biomarker in a mammal that has not been exposed to the IGF1R modulator indicates that the mammal will respond therapeutically to the method of treating cancer and (c) wherein the level of the biomarker in a mammal after exposure to a IGF1R modulator indicates that the mammal has responded therapeutically to the method of treating cancer.

Abstract: The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.

Abstract: The present invention relates to novel particles comprising polyelectrolyte polymers which are transporters of active principle (AP), in particular protein and peptide active principle, and to novel modified-release pharmaceutical formulations comprising said AP microparticles. These novel particles loaded with AP release the AP over a prolonged period of time of several days, or even several weeks.

Abstract: In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: Pharmaceutical composition comprising a chemotherapeutic agent and a TGF-beta antisense oligonucleotide, wherein the antisense oligonucleotide reduces the sensitivity and IC50, respectively, of the cytotoxicity of the chemotherapeutic agent. Preferably, the antisense oligonucleotide is a TGF-beta 1, 2, and/or 3 antisense oligonucleotide and the chemotherapeutic agent is preferably gemcitabine, 5-fluorouracil, temozolomide, dacarbacine, docetaxel, cisplatin, oxaliplatin, tamoxifen, or irinotecan.

Abstract: The present disclosure relates to amyloid beta (A?) channels and the diseases and disorders caused by abnormal activity in these channels, such as Alzheimer's disease, Lewy body dementia, inclusion body myositis, or cerebral amyloid angiopathy. The disclosure provides compositions and methods that block A? channel activity and/or reduce A?-induced toxicity in a cell. Compositions comprised of compounds having histidine coordinating capacity are used in methods to prevent, reduce, or eliminate damage caused by A? ion channels.

Abstract: A process for treating fibroses including administering a therapeutically effective amount of a pharmaceutical composition which includes at least one biocompatible polymer of the following general formula (I): AaXxYy wherein: A represents a monomer selected from the group consisting of a sugar or —(O—CH2—CH2—CO)—, X represents a carboxyl group bonded to monomer A and is contained within a group according to the following formula: —R—COO—R?, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzylamine and benzylamine sulfonate, and R? represents a hydrogen atom or a cation, Y represents a sulfate or sulfonate group bonded to monomer A and is contained within a group according to one of the following formulas: —R—O—SO3—R?, —R—N—SO3—R?, —R—SO3—R?, in which R is a bond or an aliphatic hydrocarbon chain, optionally branched and/or unsaturated, and which can contain one or more aromatic rings except for benzy

Abstract: The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide, or a fragment thereof chelated or otherwise bound to at least one active agent. Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others. Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI). Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent. Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ. If the organ is the lungs, a non-limiting example of pathology treatable with the fibrinolytic agent is pulmonary embolus.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal. Methods for modifying the genome of non-nuclear organelles are also provided.

Abstract: The invention provides nucleic acids, and variants and fragments thereof, obtained from strains of Bacillus thuringiensis encoding polypeptides having pesticidal activity against insect pests, including Coleoptera. Particular embodiments of the invention provide isolated nucleic acids encoding pesticidal proteins, pesticidal compositions, DNA constructs, and transformed microorganisms and plants comprising a nucleic acid of the embodiments. These compositions find use in methods for controlling pests, especially plant pests.

Abstract: Disclosed are a series of ?-amino-N-substituted amide compounds having a structure of the following formula, the pharmaceutically acceptable salts thereof, and the pharmaceutical composition comprising the same. The ?-amino-N-substituted amide compounds or the pharmaceutically acceptable salts thereof according to the present invention have anti-tumor and/or anti-cancer activities in vivo and in vitro, can effectively depress the growth of various tumor cells and/or cancer cells, and thus can be used in preparing drugs for treating tumors and/or cancers.

Abstract: Compositions and methods for treating ocular cancer are provided. The composition is a subconjunctival formulation of nutlin-3 and its analogs. The composition provides for methods of treating ocular cancer, including retinoblastoma. The formulation has high penetration into ocular tissue with low toxicity.

Abstract: A container containing a therapeutic protein, characterized in that chaperones molecules are bound by a molecular linker to an inner surface of the container. The linker being interposed between the surface and the chaperone.

Abstract: There are disclosed agents that inhibit Blood Brain Barrier Proteins (BBBP). Such agents are useful in controlling agents entering and exiting the CNS. This allows for drugs to be more effective and/or allowing side effects of the drugs to be lowered.

Abstract: Salp15, biologically functional equivalents and fragments thereof, and nucleic acid molecules encoding the same are disclosed. Recombinant host cells, recombinant nucleic acids and recombinant proteins are also disclosed. Salp15 gene products and Salp15 polypeptide fragments have biological activity in modulating CD4+ T cell activation through specific binding to CD4. Thus, therapeutic methods involving modulating T cell activation using Salp15 and biologically active polypeptide fragments thereof are also disclosed. The specific binding of Salp15 and fragment peptides thereof to CD4 can inhibit HIV infection of T cells, and thus methods of using Salp15 for inhibiting HIV infection are also disclosed. Screening methods for selecting substances having an ability to modulate activation of T cells are also disclosed.

Abstract: The present application provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2. In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 is also provided. Similarly, provided is a method of treating cancer in a subject by increasing expression of DEFB1 in the subject.

Abstract: The present invention relates to methods, compositions, and kits for treating or preventing symptoms of hormonal variation. The method comprises the steps of administering an effective amount of Dextromethorphan or Dextrorphan, or a pharmaceutically acceptable salt thereof, to a subject having one or more symptoms of hormonal variations.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: Disclosed are compositions and methods for diagnosing, preventing, and treating prostate cancer and prostate intraepithelial neoplasia (PIN).

Abstract: Oligonucleotide conjugates, where an oligonucleotide is covalently attached to an aromatic system, are provided. In particular embodiments the oligonucleotide is complementary to the RNA component of human telomerase and is covalently attached to a nucleobase via an optional linker. The conjugates inhibit telomerase enzyme activity.

Abstract: The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides a novel stem cell cancer marker, ALDH1, useful for the diagnosis, characterization, and treatment of solid tumor stem cells.

Abstract: The invention relates to a polysaccharide comprising carboxyl functional groups, one at least of which is substituted by a derivative of a hydrophobic alcohol. The invention also relates to a pharmaceutical composition comprising one of the polysaccharides according to the invention and at least one active principle. It also relates to a pharmaceutical composition, wherein the active principle is chosen from the group consisting of proteins, glycoproteins, peptides and nonpeptide therapeutic molecules. The invention also relates to the use of the functionalized polysaccharides according to the invention in the preparation of pharmaceutical compositions as described above.

Abstract: The invention provides methods for predicting or determining the response of a mammalian tumor to a chemotherapeutic agent and for treating a mammalian tumor comprising detecting and quantifying the SPARC protein or RNA in a sample isolated from the mammal. The invention further provides kit for predicting the response of a mammalian tumor to a chemotherapeutic agent, comprising a means for the isolation of protein or RNA from the tumor, a SPARC protein or RNA detection and quantification means, control RNAs, and rules for predicting the response of the tumor based on the level of SPARC protein or RNA in tumor.

Abstract: Proteins having the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4, or fragments of said sequences are provided. The protein fragments are represented by the sequences of SEQ ID NO: 2q, q varying from 3 to 36, and the sequences of SEQ ID NO: 185 to SEQ ID NO: 209. Nucleotide sequences coding for said proteins are also provided.

Abstract: New and improved compounds for use in radiodiagnostic imaging or radiotherapy having the formula M-N—O—P-G, wherein M is the metal chelator (in the form complexed with a metal radionuclide or not), N—O—P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and/or providing radiotherapy to a patient using the compounds of the invention are also provided. A method for preparing a diagnostic imaging agent from the compound is further provided. A method for preparing a radiotherapeutic agent is further provided.

Abstract: Compositions and methods for mucosal delivery of agents are provided. The compositions are intended for administration to mucosal surface, such as oral, gastrointestinal and nasal mucosa. The compositions provided contain one or more mucoadhesive proteins and an agent to be delivered. Methods for delivery of agents using the compositions provided herein are also provided.

Abstract: The present invention relates to the therapeutic and prophylactic use of C1 inhibitor for preventing, reducing and treating ischemia and reperfusion injury. The C1 inhibitor of the present invention is still therapeutically effective when administered after an ischemic period and reperfusion and therefore particularly useful for unforeseen occurrences of ischemic reperfusion such as e.g. a stroke.

Abstract: The invention provides methods for predicting or determining the response of a mammalian tumor to a chemotherapeutic agent and for treating a mammalian tumor comprising detecting and quantifying the SPARC protein or RNA in a sample isolated from the mammal. The invention further provides kit for predicting the response of a mammalian tumor to a chemotherapeutic agent, comprising a means for the isolation of protein or RNA from the tumor, a SPARC protein or RNA detection and quantification means, control RNAs, and rules for predicting the response of the tumor based on the level of SPARC protein or RNA in tumor.

Abstract: The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5?-(Tx)GxGxcsasasgscsastscscsTxGxT-3? and 5?-(Gx)TxTxascstsgscscststscsTxTxA-3?, wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analogue or a 2-deoxynucleotide, subscript “s” designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogues, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighboring nucleotides/LNA nucleotide analogues, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g.

Abstract: H-NOX proteins are mutated to exhibit improved or optimal kinetic and thermodynamic properties for blood gas O2 delivery. The engineered H-NOX proteins comprise mutations that impart altered O2 or NO ligand-binding relative to the corresponding wild-type H-NOX domain, and are operative as physiologically compatible mammalian blood O2 gas carriers. The invention also provides pharmaceutical compositions, kits, and methods that use wild-type or mutant H-NOX proteins for the treatment of any condition for which delivery of O2 is beneficial.

Abstract: H-NOX proteins are mutated to exhibit improved or optimal kinetic and thermodynamic properties for blood gas NO delivery. The engineered H-NOX proteins comprise mutations that impart altered NO or O2 ligand-binding relative to the corresponding wild-type H-NOX domain, and are operative as physiologically compatible mammalian blood NO gas carriers. The invention also provides pharmaceutical compositions, kits, and methods that use wild-type or mutant H-NOX proteins for the treatment of any condition for which delivery of NO is beneficial.