Abstract: Novel methods of synthesis of chelator-targeting ligand conjugates, compositions comprising such conjugates, and therapeutic and diagnostic applications of such conjugates are disclosed. The compositions include chelator-targeting ligand conjugates optionally chelated to one or more metal ions. Methods of synthesizing these compositions in high purity are also presented. Also disclosed are methods of imaging, treating and diagnosing disease in a subject using these novel compositions, such as methods of imaging a tumor within a subject and methods of diagnosing myocardial ischemia.

Abstract: Provided are methods, uses and pharmaceutical compositions for treatment of prostate cancer with a SEMA3C inhibitor in a biologically effective amount sufficient to cause cell death of a prostate cancer cell or to inhibit proliferation of the prostate cancer cells. The prostate cancer may be an androgen receptor (AR) positive prostate cancer and the SEMA3C inhibitor may be selected from one or more of the following: an antibody, a SEMA3C peptide, an antisense RNA, a siRNA, a shRNA or a small molecule.

Abstract: The invention provides methods and compositions for modulating hepsin activity and the uPA/plasmin pathway, in particular by regulating pro-uPA activation by hepsin.

Abstract: Methods are provided for inhibiting growth of prolactin-responsive cancer cells and treating prolactin-responsive malignancies via administration an agent such as cyclosporine A which directly inhibits an enzymatic activity of a cyclophilin.

Abstract: The present invention relates to novel muteins derived from human tear lipocalin. The invention also refers to a corresponding nucleic acid molecule encoding such a mutein and to a method for its generation. The invention further refers to a method for producing such a mutein. Finally, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

Abstract: The invention provides compositions comprising soluble extracts or isolated polypeptides from the edible roots of the plant Colocasia, such as Colocasia esculenta, commonly known as Taro, and from Xanthosoma, such as Xanthosoma sagittifolium, commonly known as Malanga Blanca or Yautia. The compositions exhibit inhibitory effects on metastasis of cancer cells in particular breast and prostate cancer cells and have therapeutic pharmacological activity, Pharmaceutical compositions for the treatment of cancer by inhibiting metastasis which comprises an effective amount of the described extract or isolated polypeptide thereof and optionally a pharmaceutical acceptable carrier are described.

Abstract: Lytic peptides, including fusion peptides of lytic peptides conjugated with luteinizing hormone-releasing hormone or modified versions thereof to target luteinizing hormone-releasing hormone receptors, are disclosed. The lytic peptides show anti-proliferative activity against human prostate cancer cell lines, but are nontoxic to normal primary human prostate epithelial cells or to bone marrow stromal cells in co-culture. The lytic peptides have specificity for and anti-proliferative activity against prostate cancer tumor cells, and low toxicity for normal prostate cells, making the peptides useful in therapies for prostate cancer.

Abstract: This invention is based in part on the elucidation of new structural conformations and functions of the sodium/potassium adenosine triphosphate synthase (Na/K ATPase), and especially elucidation of new binding sites and interactions. The present invention provides practical applications of several surprising structural and functional relationships between Na/K ATPase and compounds which interact with Na/K ATPase. Disclosure of these structures and relationships provides insight and practical solutions to chemically affecting not only the Na/K ATPase interactions, but also regulators known to be upstream and downstream.

Abstract: The present invention provides moieties that bind to the asymmetric contact interface of a receptor tyrosine kinase (RTK), wherein the moieties inhibit ligand induced trans autophosphorylation of the RTK. The present invention also provides methods of treating or preventing an RTK-associated disease and methods for identifying moieties that bind to an asymmetric contact interface of an RTK.

Abstract: Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical compositions containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.

Abstract: The present invention relates to a composition comprising an inhibitor of the expression or activity of SH3 domain containing ring finger 2 (SH3RF2) for preventing or treating cancers. More specifically, since the SH3RF2 protein, of which the expression level increases in various cancer tissues, binds to PAK4, which is a cancer-associated gene, to regulate an apoptosis inhibitory function of the PAK4 protein by ubiquitination activity of SH3RF2 RING domain, cancer cells, in which the expression of SH3RF2 is inhibited, sensitively respond to the induction of apoptosis to promote apoptosis and reduce in vivo tumorigenicity, such that the inhibitor of the expression or activity of SHRF2 can be useful as a composition for preventing or treating cancers.

Abstract: The present invention relates to a polypeptide capable of specifically targeting apoptotic cells undergoing apoptosis and a use thereof. More particularly, it relates to an isolated polypeptide consisting 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 and targeting apoptotic cells, a composition for detection of apoptotic cells comprising the same as an effective ingredient, a composition for drug delivery comprising the same as an effective ingredient, a composition for imaging comprising the same as an effective ingredient and the like. Accordingly, the peptide of the present invention may be useful for detection of apoptotic cells, as well as detection and imaging of apoptotic cells in tumor tissue, apoptotic myocardial cells in myocardial infarction tissue, apoptotic nerve cells in stroke tissue and arteriosclerosis site, and targeted drug delivery thereto.

Abstract: Provided is a novel, isolated polypeptide including an amino acid sequence of SEQ. ID. NO: 2 or SEQ. ID. NO: 4, and the nucleic acid molecule which encodes it. The polypeptide may be used in a method for treating various diseases including cancer, immune associated, viral and inflammatory diseases.

Abstract: Provided herein are liposomal glycolipopeptidic vaccine formulations comprising an adjuvant and an immunogen for immunotherapy and/or treatment of cancer.

Abstract: The invention provides novel peptide prodrugs that contain cleavage sites specifically cleaved by human kallikrein 2 (hK2). These prodrugs are useful for substantially inhibiting the non-specific toxicity of a variety of therapeutic drugs. Upon cleavage of the prodrug by hK2, the therapeutic drugs are activated and exert their toxicity. Methods for treating cell proliferative disorders are also featured in the invention.

Abstract: Aminoside tetracyclic anthraquinones represented by formula (I) and (II). Peptides are introduced to connect tetracyclic anthraquinones and fatty acid to enable selective absorption and release of the anticancer agents. In addition, aminosaccharide and tetracyclic moieties are introduced into the branched chain to improve water-solubility. The compounds of formula (I) and (II) are pharmaceutically active components useful for treating diseases that are cured by aminoside tetracyclic anthraquinones, including cancer.

Abstract: The present invention provides fusion proteins comprising an extracellular domain of a VEGF receptor and a death ligand. The fusion proteins bind to VEGF and to death receptors on tumor cells thereby inhibiting VEGF activation of VEGF receptors and inducing apoptosis in the tumor cells. Fusion proteins of the present invention are useful for inducing apoptosis and cytotoxic effects in cells, treating cancer and diseases or disorders related to unregulated angiogenesis and/or vasculogenesis. Thus, this invention further provides methods for treating angiogenesis related diseases using the fusion proteins, polynucleotides encoding the fusion proteins, vectors containing the polynucleotides, pharmaceutical compositions and kits containing the fusion proteins or the polynucleotides encoding the fusion proteins.

Abstract: The present invention relates to compositions comprising peptides that may be variants, derivatives and structural equivalents of cupredoxins that inhibit the development of premalignant lesions in mammalian cells, tissues and animals. Specifically, these compositions may comprise azurin from Pseudomonas aeruginosa, and/or the 50-77 residue region of azurin (p28). The present invention further relates to compositions that may comprise cupredoxin(s), and/or variants, derivatives or structural equivalents of cupredoxins, that retain the ability to inhibit the development of premalignant lesions in mammalian cells, tissues or animals. These compositions may be peptides or pharmaceutical compositions, among others. The compositions of the invention may be used to prevent the development of premalignant lesions in mammalian cells, tissues and animals, and thus prevent cancer.

Abstract: The present invention provides for a method for treating a disease condition associated with PI3-kinase ? and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase ? and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.

Abstract: The invention provides a composition comprising SGEF protein or gene as a therapeutic means to clinical or subclinical defects associated with anomalies of at least one from among the macula, corpus callosum, hippocampus, liver or immune system or feverless response to infection. Methods of diagnosis of such disease and development anomalies are based on detection of mutations of the SGEF gene. The SGEF protein is also used as a preventive or curative treatment of atherosclerosis by local or systemic delivery. The invention also provides a composition comprising an inhibitor of the SGEF gene expression or SGEF protein concentration, as a therapeutic means for glaucoma, osteoarthritis, auto-inflammatory diseases, tumors or cancers.

Abstract: The present invention provides peptides having an amino acid sequence as set forth in SEQ ID NO: 7, 8, 9, 10, 11, 12, 192, 195, 197, 209, 225, 226, 228, 230, 240, 241, 243, 244, 249, 253, 254 or 255, as well as peptides having the above-mentioned amino acid sequences in which 1, 2, or several amino acids are substituted, deleted, or added, wherein the peptides possess cytotoxic T cell inducibility. The present invention also provides drugs for treating or preventing a disease associated with the over-expression of MPHOSPH1 and/or DEPDC1, e.g. cancers, containing these peptides as an active ingredient. The peptides of the present invention can also be used as vaccines.

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: The present invention discloses: (i) two novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, and/or derivatives thereof; (ii) methods of synthesis of said novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, and/or derivatives thereof; (iii) pharmaceutically-acceptable formulations comprising said novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, derivatives thereof; and/or, optionally, one or more additional chemotherapeutic agents; and (iv) methods of administration of said novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, derivatives thereof; and/or, optionally, one or more additional chemotherapeutic agents, to subjects in need thereof.

Abstract: Methods and compositions are provided for modulating Hedgehog (Hh) pathway signaling in a cell. Aspects of the methods include methods for inhibiting Hh pathway-promoted cancer proliferation and/or metastasis that is promoted by Hh pathway signaling, methods for treating cancers promoted by Hh pathway signaling, and methods for screening candidate agents for the ability to treat a cancer promoted by Hh pathway signaling. In addition, reagents and kits thereof that find use in practicing the subject methods are provided.

Abstract: Disclosed is an isolated or purified polypeptide or peptidomimetic comprising an amino acid sequence of a portion of a Smoothened (SMO) protein, wherein the portion comprises an amino acid sequence of any of the intracellular loops of the SMO protein, a functional fragment thereof, or a functional variant of either the portion or the functional fragment, wherein the functional fragment comprises at least 7 contiguous amino acids of the intracellular loops, and wherein the functional fragment or functional variant inhibits proliferation of a diseased cell, or a fatty acid derivative thereof. Related conjugates, nucleic acids, recombinant expression vectors, host cells, and pharmaceutical compositions are further provided.

Abstract: The invention provides methods and compositions for modulating hepsin activity and the MSP/Ron pathway, in particular by regulating pro-MSP activation by hepsin.

Abstract: The present invention relates to agents for use in treating cancer. The agent to be used is an antagonist of Dsg2, wherein said antagonist modulates the function of the amino acid sequence: TQDVFVGSVEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO:1), or a fragment or variant thereof, of the EC2 domain of Dsg2. Also included in the invention are specific polypeptides and pharmaceutical preparations. Also included in the invention is a method of screening for antagonists of Dsg2, wherein said antagonist modulates the function of the amino acid sequence: TQDVFVGS VEELSAAHTLVMKINATDADEPNTLNSKISYR (SEQ ID NO: 1), or a fragment or variant thereof, of the EC2 domain of Dsg2.

Abstract: The present invention relates to methods of treating a hyperproliferative disease by administering a composition of lactoferrin alone or in combination with standard anti-cancer therapies.

Abstract: The invention relates to bifunctional stapled or stiched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stiched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stiched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stiched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Uses of the inventive bifunctional stapled or stiched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.

Abstract: The present invention relates to novel macrocyclic compounds and salts thereof that bind to and/or are inhibitors of serine protease enzymes and methods of using the compounds. The present invention also relates to intermediates of these compounds, pharmaceutical compositions containing these compounds and methods of using the same. These compounds are useful as therapeutics for treatment and prevention of a range of disease indications including hyperproliferative disorders, in particular those characterized by tumor metastasis, inflammatory disorders, skin and tissue disorders, cardiovascular disorders, respiratory disorders and viral infections.

Abstract: The disclosure provides a HER3 binding polypeptide, comprising a HER3 binding motif, BM, which motif consists of the amino acid sequence selected from i) EX2X3X4A X6X7EIW X11LPNL X16X17X18QX20 X21AFIX25 X26LX28D, and ii) an N amino acid sequence which has at least 90% identity to the sequence defined in i), wherein the polypeptide binds to the extra-cellular domain of HER3. Also provided is a bispecific ligand having binding affinity for HER3 and for HER2, or for HER3 and for EGFR, and comprising a HER3. binding polypeptide as defined herein and a HER2 binding polypeptide or a EGFR binding polypeptide.

Abstract: An object of the invention is to provide methods and compositions relating to a vaccine against prostate cancer which includes a non-human-primate PSA for administration to humans to provide an immune response against human PSA. More generally, an object of the invention is to provide methods and compositions relating to using a non-human primate xenogeneic antigen (e.g. protein) in a human, wherein, with respect to the non-human primate xenogeneic antigen that is used, there are relatively few interspecies differences between the non-human primate xenogeneic antigen and the human self antigen in order to induce an optimal immune response in the human to its native self antigen.

Abstract: The present invention is directed to methods of treating vasomotor symptoms in castrated prostatic cancer patients in need of treatment, comprising administering about 15 mg or less of cyproterone acetate per day to the patients. The present invention is further directed to dosage forms comprising about 1 mg to about 15 mg of cyproterone acetate and a package comprising a plurality of dosage forms comprising about 1 mg to about 15 mg of cyproterone acetate.

Abstract: The invention relates to methods of treatment or prophylaxis of physiological and/or pathological conditions with at least one LHRH antagonist, in particular at least one peptidomimetic LHRH antagonist such that the at least one LHRH antagonist is administered in a dose, which does not cause chemical (hormonal) castration.

Abstract: Compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and Bcl-XL are identified. These compounds have the ability to convert the activity of Bcl-2-family member proteins from anti-apoptotic to pro-apoptotic. Methods for inducing apoptosis are described, together with methods for identifying molecules that induce apoptosis through interaction with Bcl-2-family members.

Abstract: Neurotrophin binding to its specific receptors Trk A and p75 leads to the activation of multiple signalling cascades, culminating in neuroprotective and regenerative effects, including neuronal survival and neurite outgrowth. Neurotrophic factors have been used for the treatment of several neurodegenerative diseases. However, their use is limited by their inability to cross the blood-brain barrier, their short half life and their side effects. Small molecule neurotrophin mimetics may be beneficial in treating a number of neurodegenerative disorders. The present invention shows the capacity of nerve growth factor agonist molecules of Formulae I-IV, as defined in the specification, to induce differentiation in PC 12 cells, promote survival in RN22 cells and activate Trk A, IkBa and SAPK/JNK phosphorylation to various extents in both cell lines.

Abstract: Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid.

Abstract: The present invention relates to combinations of aplidine or aplidine analogues with other titumoral agents, and the use of these combinations in the treatment of cancer, in particular in the treatment of lung cancer, breast cancer, colon cancer, prostate cancer, renal cancer, melanoma, multiple myeloma, leukemia and lymphoma.

Abstract: The present application provides synbodies against AKT1 differing in amino acid sequence, conjugation chemistry, linker/scaffold, or adjunct moiety. The synbodies are useful for diagnosis and treatment of cancer and as research reagents.

Abstract: According to the invention, parvoviruses such as the adeno-associated virus Type 2 (AAV2) are found to be oncolytic, selectively mediating apoptosis in cancer cells and their precursors, while leaving healthy cells intact. The invention also includes a method of killing cancer and other neoplastic and preneoplastic cells by administrating to said cells the AAV2 proteins Rep78 or Rep 68, expression constucts encoding the same, or pharmaceutical compositions comprising the same.

Abstract: Compounds which are Spiruchostatin analogues of the general formula (I) or (I?), isosteres thereof and pharmaceutically acceptable salts thereof are found to inhibit HDAC wherein R1, R2, R3 and R4 are the same or different and represent an amino acid side chain moiety and each R6 is the same or different and represents hydrogen or C1-C4 alkyl.

Abstract: The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases, particularly pyrrolopyrimidine compounds and derivatives are described which inhibit protein kinases. The organic compounds are useful in treating proliferative disease.

Abstract: The present invention relates to chemokine-mucin fusions linked to glycosylphosphatidylinositol (GPI)-anchors and their use as anti-cancer adjuvants and as agents in tissue regeneration and suppression of vascular damage. GPI-linked chemokines are incorporated in the surface membrane of tumour cells and effect a recruitment of cytotoxic immune cells to the tumour site following injection in vivo. Leukocytes, cytotoxic T-cells and NK cells target the chemokine-GPI-anchored tumour cells and modulate cell-mediated lysis of the tumour cells. The efficiency of GPI-anchoring and modulation of immune cells can be further enhanced by linking the chemokine to a mucin domain followed by the GPI-anchor. The GPI-anchored chemokines, with or without mucin domain, are remarkably useful for the inhibition of tumour growth, tissue regeneration, and suppression of acute vascular damage to allografts.

Abstract: A method of treating cancer in a mammal is provided comprising the step of inhibiting TRIM59 expression or activity in the mammal. TRIM59 expression may also be utilized in methods of diagnosing cancer in a mammal.

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 others.

Abstract: The present invention involves the use peptides comprising ubiquitin interacting motifs (UIMs) alone or in combination with other agents to treat diseases involving neovascularization, such as cancer.

Abstract: The invention provides SPARC antisense oligonucleotides and methods of their use in proliferative diseases such as cancer and hepatic fibrosis.

Abstract: Disclosed is the use of a klotho protein or related compounds (especially KL1 or KL1 analogue) for treatment, and especially treatment of cancer, alone or together with other active pharmaceutical ingredients such as chemotherapeutic agents.

Abstract: The Wnt signaling pathways are involved in embryo development as well as in tumorigenesis. Dishevelled (Dvl) tranduces Wnt signals from the receptor Frizzled (Fz) to downstream components in canonical and non-canonical Wnt signaling pathways, and the Dvl PDZ domain plays an essential role in both pathways, and the Dvl PDZ domain binds directly to Fz receptors. In the present invention using NMR-assisted virtual ligand screening, several compounds were identified and were found to bind to the Dvl PDZ domain. Molecular dynamics simulation was used to analyze the binding between the PDZ domain and these compounds in detail. These compounds provide a basis for rational design of high-affinity inhibitors of the PDZ domain, which can block Wnt signaling by interrupting the Fz-Dvl interaction.

Abstract: Disclosed is the use of a klotho protein or related compounds for the diagnosis and treatment of cancer, alone or together with other active pharmaceutical ingredients such as chemotherapeutic agents or hormone-regulating agents.