Abstract: Characteristics of the VSELs stem cell population of a mammal are correlated with aging, including VSEL number, imprinting status of genetic loci, and expression of markers of pluripotent stem cells. The present invention provides VSEL-based methods and compositions for determining the biological age of a mammal.

Abstract: A vaccine is disclosed that promotes CD4+ T cell-independent host defense mechanisms to defend against infection by fungi such as Pneumocystis spp. The vaccine may be used to prevent or to treat fungal infections. The novel vaccine can provide protective immunity, even for immunocompromised individuals such as HIV patients having reduced levels of CD4+ T cells.

Abstract: The present invention provides conjugates of cytokines and targeting peptides that is able to bind to a receptor expressed on tumor-associated vessels or to a component of the extracellular matrix associated to the tumor vessels, for treatment of malignant pleural mesothelioma. In particular, the invention provides conjugates comprising the cytokine TNF linked to a peptide containing the NGR motif. The invention further provides pharmaceutical compositions comprising such conjugate and pharmaceutical formulations comprising conjugates dissolved in appropriate buffers.

Abstract: The present invention relates to immunotherapeutic peptides and their use in immunotherapy, in particular the immunotherapy of cancer. The present invention discloses tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor immune responses. In particular, the composition of the peptides of the present invention can be used in vaccine compositions for eliciting anti-tumor immune responses against gliomas.

Abstract: The present invention relates to pharmaceutical formulations suitable for targeting particular tissue and/or organ(s) with a formulated active ingredient, for example when administered upstream of the target organ or tissue, and to use of the same in treatment, methods of treatment administering the same and methods of preparing the formulations. The pharmaceutical formulations of the invention are for parenteral administration to a target tissue and comprise particles containing an active ingredient, and a biodegradable excipient, wherein 90% or more of the particles have a diameter of between 10 and 20 microns and the formulation is substantially free of particles with a diameter greater than 50 microns and less than 5 microns, such that where the formulation is administered upstream of the target tissue the ability of the active to pass through the target tissue and pass into systemic circulation is restricted.

Abstract: Improved (safer and more effective) methods of therapy using TNF-R agonists, e.g., CD40 agonists are provided. These methods provide for the addition of an amount of a type 1 interferon and/or a TLR agonist that is effective to prevent or reduce the toxicity (liver toxicity) that may otherwise result in some patients of the TNF-R agonist is used as a monotherapy (without the type 1 interferon and/or TLR agonist).

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: The present invention provides therapeutic agents for diseases associated with skeletal muscle degeneration comprising a granulocyte colony-stimulating factor (G-CSF) as an active ingredient. The therapeutic agents of the present invention are especially effective as therapeutic agents for muscular dystrophy.

Abstract: Compositions for use in treatment of a variety of tissue diseases include stem cells and stem cell released molecules (SRM's) suspended in an aqueous solution with a cellulosic material or other thickening agent. The stem cells and SRM's can be derived from one or more distinct cell lines. The SRM's can further include one or more mucins, cytokines, or growth factors. Exemplary formulations include stem cells and SRMs derived from epithelial stem cells, corneal limbal stem cells, and fibroblasts. Other compositions and methods for formulation thereof are described.

Abstract: The present invention relates to muscle repair promoters for local application that contain a colony-stimulating factor (CSF) as an active ingredient. The muscle repair promoters of the present invention exhibit their effect at low doses, particularly when they are administered intramuscularly.

Abstract: The present invention provides a new stable pharmaceutical composition of granulocyte-colony stimulating factor (G-CSF).

Abstract: Disclosed are compositions and methods comprising combinations of anti-CD74 antibodies with a therapeutic agent that is attached to the anti-CD74 antibody or separately administered. Preferably, the therapeutic agent is an antibody that binds to an antigen different from CD74, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80, IL-6, CXCR4 or HLA-DR. However, the therapeutic agent may be an immunomodulator, a cytokine, a toxin or other known therapeutic agent. Preferably, the anti-CD74 antibody is part of a DNL complex. More preferably, combination therapy with the anti-CD74 antibody and therapeutic agent is more effective than antibody alone, therapeutic agent alone, or the combination of unconjugated anti-CD74 antibody and therapeutic agent. Administration of combination induces apoptosis of target cells in diseases in which CD74 is overexpressed, such as solid tumors, B-cell lymphomas or leukemias, autoimmune disease, immune dysfunction disease or diabetes.

Abstract: A medicament having a higher therapeutic effect than that provided by administration of a recombinant antibody against human CC chemokine receptor 4 or an antibody fragment thereof or an agent alone is provided.

Abstract: The present invention relates to vaccines comprising at least one mRNA encoding at least one antigen for use in the treatment of a disease in an elderly patient preferably exhibiting an age of at least 50 years, more preferably of at least 55 years, 60 years, 65 years, 70 years, or older, wherein the treatment comprises vaccination of the patient and eliciting an immune response in said patient. The present invention is furthermore directed to kits and kits of parts comprising such a vaccine and/or its components and to methods applying such a vaccine or kit.

Abstract: The present invention belongs to the field of the application of genetic engineering and gene function, and it is directed to a new medical use of the gene encoding the recombinant soluble tumor necrosis factor ? receptor (HusTNFR). The present invention made intervention to fulminant hepatic failure in mice by use of the long-acting recombinant human soluble tumor necrosis factor ?receptor and the classic animal models of acute and sub-acute hepatic failure. The results showed that the long-acting soluble tumor necrosis factor ?receptor of the present invention has a half-life extended more than 10 times, and it significantly decreased the mortality of model animals and has superior therapeutic effect for the treatment and/or prophylaxis of acute and sub-acute hepatic failure in model animals. These receptors have a noticeable therapeutic effect for the treatment and/or prophylaxis of acute and sub-acute hepatic failure in comparison with the non-long-acting HusTNFR.

Abstract: The present invention provides antigen-specific, tolerance-inducing microparticles for the targeted delivery of therapeutic agents to immune cells. In addition, the present invention allows for sustained release of therapeutic agents for a prolonged period of time. Also provided are therapeutic uses of the present invention for the prevention and/or treatment of immune diseases and autoimmune disorders. In a specific embodiment, the present invention provides treatment for type 1 diabetes.

Abstract: A flowable biomedical implant for application to a bone defect to promote bone growth is provided. The flowable biomedical implant comprises a carrier matrix including a biodegradable polysaccharide and ceramic material. An impermeable membrane can be integrally formed at the surface of the carrier matrix by applying a crosslinking agent to the biodegradable polysaccharide mixed with ceramic materials.

Abstract: The described invention provides methods and regimens for treating adverse consequences of a persistent and progressive myocardial injury-due to a vascular insufficiency that occurs early or late in a subject in need thereof, and progressive myocardial injury-preventing compositions that contain a chemotactic hematopoietic stem cell product, and, optionally, an additional active agent. The method treats ongoing vascular insufficiency affecting coronary circulation by (i) stimulating neoangiogenesis in a peri-infarct border zone, thereby improving myocardial perfusion; and, (ii) through a paracrine effect, preventing apoptosis of cardiomyocytes in the peri-infarct border zone. The neoangiogenesis and paracrine-mediated reduction of apoptosis reduces progressive myocardial cell loss, which leads to improvement in cardiac function and a reduction of risk of major adverse cardiovascular events.

Abstract: Compositions for activating SGK-1 are provided. SGK-1 activators can be identified by the methods of screening provided herein. The SGK-1 activators can be used in the disclosed methods of reducing cell death and methods of treating ischemic-reperfusion injury. The ischemic-reperfusion injury can be due to a variety of complications resulting in blood loss to tissue and then the re-establishment of blood flow to the tissue.

Abstract: Disclosed are water soluble polymeric conjugates comprising the structure POLY-[Y—S—S-A]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 2, S—S is a disulfide group attached to an sp3 hybridized carbon of Y; and A is a covalently linked residue of a pharmacologically active molecule. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are polymeric reagents useful to prepare such conjugates, and methods of their formation and use.

Abstract: Methods and kits for preventing or reducing the likelihood of implantation failure or miscarriage in a recipient of artificial insemination are provided. The methods include administering into a recipient of artificial insemination in need of such treatment an effective amount of granulocyte colony stimulating factor (G-CSF).

Abstract: Provided are pharmaceutical liquid formulations of G-CSF, which are stable over a long time period and substantially free of excipients, as well as ready-to-use syringes containing such formulations and corresponding kits.

Abstract: Compositions and methods for immunization against human breast cancer are disclosed. In one embodiment the multivalent antigenic composition is provided comprising immunogenic polypeptides selected from the group consisting of human ?-lactalbumin, ?S1 casein, ?-casein and ?-casein.

Abstract: A composition for treating a wound, wherein the composition can comprise therapeutically effective amount of an epidermal growth factor and a physiologically acceptable agent, wherein the physiologically acceptable agent comprises at least one of a stabilizer, a preservative, a thickening agent, carrier/diluent, and optionally pH regulating agent and humectant.

Abstract: A novel nucleic acid construct for down-regulating angiogenesis in a tissue of a subject is provided. The nucleic acid construct includes: (a) a first polynucleotide region encoding a chimeric polypeptide including a ligand binding domain fused to an effector domain of an apoptosis signaling molecule; and (b) a second polynucleotide region encoding a cis acting regulatory element being for directing expression of the chimeric polypeptide in a specific tissue or cell; wherein the ligand binding domain is selected such that it is capable of binding a ligand present in the specific tissue or cell, whereas binding of the ligand to the ligand binding domain activates the effector domain of the apoptosis signaling molecule. Also provided are methods of utilizing this nucleic acid construct for treating diseases characterized by excessive or aberrant neo-vascularization or cell growth.

Abstract: The present application provides compositions and methods useful for treating and diagnosing diseases and disorders associated with moesin activation.

Abstract: Granulocyte colony-stimulating factor (G-CSF; a stem cell enhancer and facilitator), DETC-MeSO (a glutamate receptor partial antagonist and anti-excitotoxicity agent), and sulindac (a potent anti-oxidant and anti-inflammatory agent) each can protect brain tissue exposed to a cerebral ischemia/reperfusion injury, and minimize the size of infarcts that develop as a result of the injury. When administered in combination, these agents are effective at protecting brain tissue and minimizing the size of an infarct resulting from the injury at much lower concentrations compared to using a single agent.

Abstract: A method for enhancing bone marrow cells, peripheral blood, and umbilical cord blood engraftment is disclosed wherein at least one of a granulocyte colony stimulating factor and a granulocyte macrophage colony stimulating factor, and optionally romiplostim, and optionally an erythropoiesis-stimulating agent, are added thereto for enhancing the engraftment of CD44 cells within the bone marrow cells, peripheral blood, and umbilical cord blood. Also provided is a method for enhancing a stem cell infusion by activating an up-regulation of a AF1q/CD44 signaling pathway. A stem cell product is disclosed having treated stem cells conditioned for activating an up-regulation of a AF1q/CD44 signaling pathway.

Abstract: Multifunctional polymers are disclosed having a smart segment and a biodegradable segment. Advantageously, the biodegradable segment includes a hydrophilic segment and a hydrophobic segment. Embodiments include combining the multifunctional polymeric material with a biologically active substance in an aqueous loading environment and administering the composition as a drug delivery vehicle to a human subject.

Abstract: A method of treating endothelial cells comprising: inducing vasodilation in a patient; and administering a composition including a stem cell proliferation agent to the patient.

Abstract: It is disclosed herein that osteoprotegerin increases human beta cell proliferation and survival. Methods are provided for increasing beta cell proliferation, but contacting a beta cell with an effective amount of osteoprotegrin, a functional fragment, variant or fusion protein thereof. Methods are also provided for treating a human subject with diabetes, comprising administering to the subject a therapeutically effective amount of osteoprotegerin, functional variant or fusion protein thereof.

Abstract: A method, and system, to induce remission in diseases characterized by excess production of sTNR and interleukin 2 has been developed. In the most preferred embodiment, the system consists of antibodies to sTNFR1, sTNFR2 and sIL2R immobilized in a column containing a material such as SEPHAROSE™. The patient is connected to a pheresis machine which separates the blood into the plasma and red cells, and the plasma is circulated through the column until the desired reduction in levels of sTNFR1, sTNFR2, and IL2 is achieved, preferably to less than normal levels. In the preferred method, patients are treated three times a week for four weeks. This process can be repeated after a period of time. Clinical studies showed reduction in tumor burden in patients having failed conventional chemotherapy and radiation treatments.

Abstract: Compositions for forming a self-reinforcing composite biomatrix, methods of manufacture and use therefore are herein disclosed. Kits including delivery devices suitable for delivering the compositions are also disclosed. In some embodiments, the composition can include at least three components. In one embodiment, a first component can include a first functionalized polymer, a second component can include a second functionalized polymer and a third component can include silk protein or constituents thereof. In some embodiments, the composition can include at least one cell type and/or at least one growth factor. In some embodiments, the composition can include a biologic encapsulated, suspended, disposed within or loaded into a biodegradable carrier. In some embodiments, the composition(s) of the present invention can be delivered by a dual lumen injection device to a treatment area in situ, in vivo, as well as ex vivo applications.

Abstract: The present invention relates generally to the treatment of an interleukin-11 (IL-11)-mediated condition. More particularly, the present invention provides the use of modified forms of IL-11 which modulate IL-11 signaling in the treatment of IL-11-mediated conditions.

Abstract: Compositions and methods of activating dendritic cells with LMP1 and LMP1-activated dendritic cell based compositions and methods are effective for dendritic cell therapy and provide an adjuvant function for vaccine administration. LMP1 or LMP1-CD40 chimeric protein may be used to activate and mature dendritic cells. LMP1 and LMP1-activated dendritic cells act as an adjuvant to enhance the cellular immune response. Also disclosed herein are kits for activating dendritic cells and for preparing a vaccine formulation. Administration of the dendritic cells transfected with LMP1 can induce an immune response against cancer or infection. The mature dendritic cells may comprise an antigen and at least one cytokine in addition to LMP1.

Abstract: Peptide of a size comprised between 5 and 40 amino acids, originating from a cytokine, in which at least one of its amino acids comprises at least one of its atoms separated by a distance d of less than 5 angströms from an atom of the receptor corresponding to said cytokine, the spacing d being evaluated on the basis of structural data, derivatives, immunogenic compounds comprising them, use of a peptide or peptide derivative or immunogenic compound for the preparation of a curative or preventative medicament intended for the treatment or prevention of diseases linked to an excess or to the presence of cytokines or for the treatment of an auto-immune disease and pharmaceutical compositions which contain at least one abovementioned peptide or peptide derivative or immunogenic compound as active ingredient.

Abstract: The present invention provides methods for treating a patient undergoing multi-cycle chemotherapy that provides significantly improved platelet counts in the patients, and facilitates retention of dose intensity from cycle to cycle of the chemotherapy.

Abstract: This invention provides novel carbonic anhydrase (CAIX) nucleic acid and peptide sequences, as well as related methods and compositions, including anti-cancer immunogenic agent(s) (e.g. vaccines and chimeric molecules) that elicit an immune response specifically directed against cancer cells expressing a CAIX antigenic marker. The novel CAIX variant and related compositions are useful in a wide variety of treatment modalities including, but not limited to protein vaccination, DNA vaccination, adoptive immunotherapy.

Abstract: Embodiments herein concern compositions and methods for treating a subject having or suspected of developing a pulmonary disorder or cancer. Certain embodiments concern modulating protein tyrosine phosphatase non-receptor type 13 (PTP-N13) expression and/or activity in a subject to treat uncontrolled cellular growth in the subject.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: The present invention provides, in part, MCP1-Ig fusion polypeptides exhibiting surprisingly beneficial properties as well as methods for treating various diseases (e.g., inflammatory diseases) by administering any of such fusions.

Abstract: Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.

Abstract: The present invention provides a tumor cell-soluble TNF family member molecule complex containing a tumor cell and an isolated soluble TNF family member molecule, wherein the soluble TNF family member molecule is bound on a surface of the tumor cell such that it binds to a receptor of the TNF family member expressed on a surface of a cell other than the tumor cell, and stimulates the cell other than the tumor cell via the receptor, and a composition and a tumor vaccine, each containing the complex.

Abstract: A therapeutic or prophylactic treatment method of ischemia, such as due to myocardial infarction, by administering thrombopoietin, alone or in combination with other drugs, to a patient suffering from or at risk of cardiac injury, such as myocardial ischemia. The thrombopoietin is administered in a concentration such that the subject's platelet count or production of platelets is not significantly affected.

Abstract: The present invention relates to skin care compositions, including cosmeceuticals, for topical application, and more particularly, a skin cream, comprising cell culture medium conditioned by cells grown in two-dimensional culture. Also included are methods of using such compositions and kits comprising the skin cream therein.

Abstract: Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Abstract: The present invention provides methods and agents for the treatment of TWEAK-related conditions, including cardiac, liver, kidney, lung, adipose, skeletal, muscle, neuronal, bone and cartilage conditions. The invention also provides methods for identifying TWEAK agonists or antagonists for the treatment of TWEAK-related conditions. Additionally, the invention provides transgenic animals that express an exogenous DNA encoding a TWEAK polypeptide, or fragments, analogs, or muteins thereof, and methods for using such animals to identify TWEAK agonists or antagonists. The invention further provides methods for diagnosing a disease based on TWEAK expression. The invention also provides methods for affecting cellular differentiation of progenitor cells using TWEAK polypeptides, agonists, or antagonists.

Abstract: The invention relates to the field of treatment of ischemic conditions and diseases using a cell population comprising CD34+ cells isolated from peripheral blood of a subject. The invention provides a pharmaceutical composition comprising (i) a cell population comprising CD34+ cells, (ii) a plasma protein, and (iii) an isotonic solution comprising at least one salt, said isotonic solution comprising acetate, gluconate, or both acetate and gluconate. Methods of treating tissue damaged by ischemia in a subject and methods of treating a medical condition, wherein the pharmaceutical composition of the invention is administered, are further provided herein. Also, methods of promoting mobilization of CD34+ cells from bone marrow into peripheral blood are provided herein.

Abstract: Therapeutic peptide compositions comprise a therapeutic peptide, such as insulin, together with an alkyl N,N-disubstituted amino acetate, such as dodecyl 2-(N,N-dimethylamino) propionate.

Abstract: Compounds having the formula (I) wherein R1, R2, R3 and X are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.