Abstract: The present invention is directed to a combination comprising a proteasome inhibitor and a compound of formula I or a pharmaceutically acceptable salt thereof: to a pharmaceutical composition and to a kit both comprising said combination, to the combination, composition or kit for use in the treatment of cancer, and to a method of treatment of cancer in a patient in need thereof comprising administering to said patient an effective amount of said combination, composition or kit.

Abstract: The present invention is directed to a combination comprising a proteasome inhibitor and a compound of formula I or a pharmaceutically acceptable salt thereof: to a pharmaceutical composition and to a kit both comprising said combination, to the combination, composition or kit for use in the treatment of cancer, and to a method of treatment of cancer in a patient in need thereof comprising administering to said patient an effective amount of said combination, composition or kit.

Abstract: The invention relates among others to antibodies comprising a first antigen-binding site that binds Erb B-2 and a second antigen-binding site that binds Erb B-3. The antibodies can typically reduce a ligand-induced receptor function of Erb B-3 on a Erb B-2 and Erb B-3 positive cell. Also described are method for the treatment and use of the antibodies in imaging and in the treatment of subjects having an Erb B-2, Erb B-3 or Erb B-2/3 positive tumor.

Abstract: SIRP1alpha-41BBL fusion proteins are provided. Accordingly, there is provided a SIRPalpha-41BBL fusion protein comprising a single amino acid linker between the SIRPalpha and the 41BBL. Also there is provided a SIRPalpha-41BBL fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRP1alpha-41BBL fusion protein, host-cells expressing the SIRP1alpha-41BBL fusion protein and methods of use thereof.

Abstract: Provided are compositions and methods for prophylaxis and/or therapy of ErbB2-positive cancer. The compositions include pharmaceutical preparations that contain isolated or recombinant or modified peptidase D (PEPD) proteins. The methods include prophylaxis and/or therapy of ErbB2-positive cancer by administering a PEPD to an individual who has or is at risk for developing ErbB2-positive cancer.

Abstract: Disclosed herein are embodiments of a donor compound that releases COS and/or CS2, which can be converted to H2S. The donor compound embodiments described herein can be used to deliver H2S to a subject or a sample and further can be used to administer therapeutic agents. Methods of making and using the donor compound embodiments also are disclosed.

Abstract: The success of anti-tumor immune responses requires effector T cells to infiltrate solid tumors, a process guided by chemokines. Herein, we demonstrate that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10, and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide the first direct in vivo evidence for controlling lymphocyte trafficking through CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing the biologically active form of chemokines as a strategy to enhance tumor immunotherapy.

Abstract: The embodiments include methods of ameliorating or preventing the worsening or progression and/or ameliorating or preventing the worsening or lack of improvement of symptoms of BPH in mammals, using compositions containing compounds based on small peptides and a pharmaceutically acceptable carrier. The method includes, but is not limited to, administering the compounds intramuscularly, orally, intravenously, intraprostatically, intrathecally, intratumorally, intranasally, topically, transdermally, etc., either alone or conjugated to a carrier to a mammal in need thereof.

Abstract: The present disclosure provides formulations for pharmacologically active reagents, including formulations based on particulates formed from a biodegradable polymer (e.g., a polysaccharide such as dextran) linked to a vitamin or related agent (e.g., folic acid). Hydrophobic pharmaceutically active agents (such as anti-cancer drugs, e.g., paclitaxel) are encapsulated into the polysaccharide-vitamin conjugate for the administration of paclitaxel. The active agent is in a core portion of the particulate, instead of on the surface of the particulate. Processes for making and using the particulates and compositions comprising the same are also disclosed. In particular, methods of cancer diagnosis and treatment are provided.

Abstract: Provided are compositions and methods for prophylaxis and/or therapy of ErbB2-positive cancer. The compositions include pharmaceutical preparations that contain isolated or recombinant or modified peptidase D (PEPD) proteins. The methods include prophylaxis and/or therapy of ErbB2-positive cancer by administering a PEPD to an individual who has or is at risk for developing ErbB2-positive cancer.

Abstract: The present invention provides cyclic nitro compound, pharmaceutical compositions of cyclic nitro compounds and methods of using cyclic nitro compounds and/or pharmaceutical compositions thereof to treat or prevent diseases or disorders characterized by abnormal cell proliferation, such as cancer, inflammation, cardiovascular disease and autoimmune disease.

Abstract: The present disclosure relates to novel compounds, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of estrogen-related diseases and conditions.

Abstract: Disclosed are pharmaceutical and synergistic compositions human recombinant alpha-fetoprotein expressed in eukaryotic cells for preparation of therapeutic agents for use in oncology, immunotherapy, stem cell therapy, and cosmetology and also for the diagnosis of cancer and embryogenic pathologies.

Abstract: The present specification provides immunosuppressive Tat derivative polypeptides, compositions, and methods of using such polypeptides and compositions to treat an autoimmune disease, an inflammation-associated disease and/or a neurodegenerative disease.

Abstract: Provided herein are SIRP-gamma, SIRP-beta or SIRP-beta2 decoy polypeptides for immunotherapy and/or treatment of cancer, anemia, transplant, asthma, allergy, auto-immune disease, and viral infection.

Abstract: The invention features methods to induce and maintain a protective cytotoxic T-lymphocyte response to a peptide of the HER2/neu oncogene, E75, with the effect of inducing and maintaining protective or therapeutic immunity against breast cancer in a patient in clinical remission. The methods comprise administering to the patient an effective amount of a vaccine composition comprising a pharmaceutically acceptable carrier, an adjuvant such as recombinant human GM-CSF, and the E75 peptide at an optimized dose and schedule. The methods further comprise administering an annual or semi-annual booster vaccine dose due to declining E75-specific T cell immunity. The invention also features vaccine compositions for use in the methods.

Abstract: The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for NY-ESO-1. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a mammal and a method of treating or preventing cancer in a mammal using the inventive TCRs or related materials.

Abstract: Peptide compounds derived from human melanotransferrin, and compositions thereof, are described. Uses of these peptide compounds, for example to modulate angiogenesis and/or cell migration, and/or to treat angiogenesis-related disorders (e.g., cancer), are also described.

Abstract: The present invention relates to a method of treating cancer in a human and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering a proteasome inhibiting compound, and N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide, or a pharmaceutically acceptable salt thereof, and optional additional antineoplastic agents, to a human in need thereof.

Abstract: Methods are presented for the therapeutic administration of angiocidin in the treatment of cancers such as glioma, breast cancer, and leukemia. Methods are also presented for inducing growth arrest and/or apoptosis of tumor cells, as well as inducing differentiation of tumor cells to inhibit tumorigenicity and to confer a non-tumor or healthy phenotype.

Abstract: A method for treating cancer, preventing cancer or delaying the progression of a cancer in an animal or human comprising the step of: administering to the animal or the human having a cancer a composition in an amount effective to treat cancer, prevent cancer or delay the progression of cancer in the animal or the human. The composition comprises a pharmaceutically acceptable excipient, and ascorbate which is joined to a carrier structure containing an anti-cancer active agent, said carrier structure being capable of releasing the anti-cancer agent in the presence of a reactive oxygen species.

Abstract: A leucine zipper variant, a polynucleotide encoding the leucine zipper variant, a method of preparing a leucine zipper variant, a method of inhibiting HDM2- and/or HDMX using the leucine zipper variant, and a method of the prevention and/or treatment of cancer using the leucine zipper variant.

Abstract: Described herein is an isolated polypeptide which is capable of specifically targeting apoptotic cells undergoing apoptosis and consists of the sequence (I): Cys-X1-Val-Ala-Pro-X2 (I), wherein X1 is an amino acid with polar uncharged side chain and X2 is an amino acid with positive charged side chain. The isolated polypeptide of the present invention may be useful for detecting apoptotic cells, as well as detecting and imaging apoptotic cells in tumor tissue, apoptotic myocardial cells in myocardial infarction tissue, apoptotic nerve cells in stroke tissue, and arteriosclerosis site; the polypeptide is useful for targeted drug delivery thereto.

Abstract: Template-fixed ?-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties These ?-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Abstract: This application is directed to chemokine-immunoglobulin fusion polypeptides and chemokine-polymer conjugates. The fusion polypeptides and conjugates can be used for treating chemokine receptor-mediated disorders and modulating inflammation, inflammatory cell motility, cancer cell motility, or cancer cell survival.

Abstract: This invention relates to an isolated, compound of Formula (1) or derivatives or pharmaceutically acceptable salts thereof. The invention also includes all isomeric and tautomeric forms of the compound of Formula (1) or the derivatives thereof. The present invention further relates to processes for the production of the compound of Formula (1) by fermentation of the fungal strain of Actinomycetes (PM0895172/MTCC 684), pharmaceutical compositions comprising the compound of Formula (1) as the active ingredient; and use of the compounds or composition containing them in the treatment of cancer.

Abstract: Disclosed are amphiphilic peptides. Also disclosed are methods of treating proliferative disease, bacterial infection, viral infection and fungal infection, endotoxin neutralization and a method of removing biofilm. Also disclosed is the use of the amphiphilic peptides.

Abstract: A method for determining whether early stage cancer is present in a subject comprises detecting the expression level of GASP-1 in the subject by detecting the amount of GASP-1 peptide fragments present in a biological sample of the subject. Because cancer can be detected at an early stage, therapeutic targeting may be initiated before cancer reaches late stage (e.g., before the development of overt symptoms). A method for treating early stage cancer in a subject comprises administering to the subject an effective amount of a GASP-1 inhibitor to inhibit the progression of early stage cancer to late stage cancer. A Competitive ELISA capable of detecting GASP-1 peptide fragments at a concentration of less than 1 ng/ml was developed.

Abstract: Disclosed are: a peptide comprising an amino acid sequence composed of contiguous nine amino acid residues derived from a WT1 protein, wherein an amino acid residue at position 2 in the amino acid sequence is selected from the group consisting of Ala, Ile, Leu, Val, Phe, Tyr, Ser and Asp and an amino acid residue at position 9 in the amino acid sequence is Arg; a polynucleotide encoding the peptide; a pharmaceutical composition comprising the peptide; and a method of treating cancer using the peptide.

Abstract: The present invention relates to a method of modulating Na+/K+ pump activity, the method comprising contacting the Na+/K+ pump with an FXYD protein or a fragment or variant thereof wherein glutathionylation of said Na+/K+ pump is altered by said FXYD protein.

Abstract: This relates to the prevention of cancer initiation. More specifically, the invention provides compositions and methods useful for altering the genetic signature in breast tissue, said alteration being correlated with a reduced risk for the development of breast cancer.

Abstract: The present invention relates to methods, compositions, and diagnostic tests for treating and diagnosing proliferative disorders, such as cancel-, that result in dysregulation of malic enzyme 2. In particular, the methods and compositions include monotherapy with malate, or a derivative thereof, as well as combination therapy, such as malate, or a derivative thereof, combined with another therapeutic agent, such as a malic enzyme 2 inhibitor, an antineoplastic agent, a glycolysis inhibitor, an antiangiogenic agent, an immunomodulatory agent, an antibody, or a cytokine.

Abstract: Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Abstract: The present invention provides biologically active peptidomimetic macrocycles for the treatment of cell proliferative disorders such as cancer and immunoproliferative disease.

Abstract: The present invention relates to novel agents, pharmaceutical compositions containing them, and theft use in therapy, particularly anti-microbial and anti-cancer therapy. In particular, the present invention relates to novel peptide-based compounds based on SEQ ID NO: 40 which have surprisingly been shown to have inhibitory effects on the growth and/or viability of cells, particularly bacterial and cancer cells. Also provided are therapeutic and non-therapeutic methods which include the use of peptides of the invention.

Abstract: Disclosed are: a peptide comprising an amino acid sequence composed of contiguous nine amino acid residues derived from a WT1 protein, wherein an amino acid residue at position 2 in the amino acid sequence is selected from the group consisting of Ala, Ile, Leu, Val, Phe, Tyr, Ser and Asp and an amino acid residue at position 9 in the amino acid sequence is Arg; a polynucleotide encoding the peptide; a pharmaceutical composition comprising the peptide; and a method of treating cancer using the peptide.

Abstract: A method of diagnosing metastatic potential of a breast cancer in an individual with breast cancer is described. The method comprises a step of assaying a breast cancer tumour sample from the patient for expression of ADAM22, wherein expression of ADAM22 correlates with increased potential for metastasis compared with a patient who is ADAM22 negative. The invention also describes an agent for use in the treatment of metastatic breast cancer in a patient, in which the agent is selected from LGI1 protein (SEQ ID NO:1) and an LGI1 peptide mimic capable of mimicking the ADAM22 binding activity of LGI1 by binding to the LGI1 binding domain of ADAM22 (SEQ ID NO: 4) and which is capable of inhibiting migration of endocrine resistant breast cancer cells.

Abstract: The present invention provide purified Flt4 receptor tyrosine kinase polypeptides and fragments thereof, polynucleotides encoding such polypeptides, antibodies that specifically bind such polypeptides, and uses therefor.

Abstract: Disclosed are: a peptide comprising an amino acid sequence composed of contiguous nine amino acid residues derived from a WT1 protein, wherein an amino acid residue at position 2 in the amino acid sequence is selected from the group consisting of Ala, Ile, Leu, Val, Phe, Tyr, Ser and Asp and an amino acid residue at position 9 in the amino acid sequence is Arg; a polynucleotide encoding the peptide; a pharmaceutical composition comprising the peptide; and a method of treating cancer using the peptide.

Abstract: Heteroaryl pyridone and aza-pyridone amide compounds of Formula I are provided, and various substituents including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk, and for treating cancer and immune disorders such as inflammation mediated by Btk. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Abstract: The invention provides human secreted proteins (SECP) and polynucleotides which identify and encode SECP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of SECP.

Abstract: The present invention relates to heterogeneous or artificially created forms of plant defensins, and to uses of such heterogenous or artificially created defensins including methods for preventing or treating proliferative diseases. Compositions for use as animal and human medicaments are also provided. The present invention also relates to associated methods, uses, systems and kits.

Abstract: The invention relates to methods for producing papilloma-derived nanosphere particles that contain therapeutic, diagnostic, or other agents. The invention also provides nanosphere particle preparations that are useful for selectively delivering therapeutic, diagnostic, and/or other agents to cancer cells of subjects without eliciting a serotype-specific immunogenic response in the subjects.

Abstract: Methods of inhibiting the Hsp90 chaperone pathway including contacting one or more target cells with an effective amount of a naturally occurring beauvericin, a synthetic beauvericin, or a derivative, analog or prodrug, or a pharmacologically active salt thereof to reduce, decrease, or inhibit the Hsp90 chaperone pathway in the cells compared to a control are disclosed. The methods can reduce the viability of the target cells, for example, by increasing apoptosis or pro-apoptotic pathways. In preferred embodiments, the methods reduce or do not increase Hsp70, Hsp24, Hsp40, or HOP expression; reduce or do not increase the heat shock response; reduce or do not increase pro-survival pathways in the cells. Methods of treating diseases such as cancer, inflammatory diseases or disorders, neurodegenerative diseases, and infectious diseases using the disclosed compositions and methods are also disclosed.

Abstract: The invention provides compositions and methods for treating breast cancer. Specifically, the invention relates to administering a Transforming Growth Factor beta (TGF?) antagonist in combination with capecitabine and ixabepilone to treat breast cancer.

Abstract: The invention relates to a cell-penetrating peptide, optionally linked to a pro-apoptotic peptide, useful as pro-apoptotic agents, for inhibition of in vitro cell proliferation and for treatment of tumors.

Abstract: The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

Abstract: The invention provides di-peptide conjugated antitumor agents, pharmaceutical compositions and methods for preparation and use thereof for treating various cancer and inflammation-related diseases and conditions. The present invention addresses the shortcomings of the existing anti-tumor and anti-inflammatory drugs, particularly in that the anti-tumor agents of the invention that selectively kill cancer cells with minimal damage to normal cells.

Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.