Abstract: The invention relates to a pharmaceutical combination which comprises (a) a DNA topoisomerase inhibitor compound and (b) a compound that inhibits the caspase-9 inhibiting properties of an inhibitor of apoptosis protein (IAP) for the treatment of a proliferative disease, especially a solid tumor disease; a pharmaceutical composition comprising such a combination; the use of such a combination for the preparation of a medicament for the treatment of a proliferative disease; a commercial package or product comprising such a combination as a combined preparation for simultaneous, separate or sequential use; and to a method of treatment of a warm-blooded animal, especially a human.

Abstract: A purified polypeptide includes an amino acid sequence consisting of about 10 to 80 amino acids, the amino acid sequence having a sequence identity at least 90% homologous to a portion of SEQ ID NO:1. The polypeptide inhibits binding of Bcl-2 to IP3 receptors of cells that express IP3R and Bcl-2 and induces apoptosis in a cell.

Abstract: The present invention provides novel salts and solvates of macrocyclic compounds that bind to and/or are functional agonists of the ghrelin (growth hormone secretagogue) receptor. The invention also relates to polymorphs of these salts and solvates, pharmaceutical compositions containing these salts or solvates, and methods of using the pharmaceutical compositions. These pharmaceutical compositions are useful as therapeutics for a range of disease indications, in particular, for treatment and prevention of gastrointestinal disorders including, but not limited to, postoperative ileus, gastroparesis, including diabetic and postsurgical gastroparesis, opioid bowel dysfunction, chronic intestinal pseudo-obstruction, short bowel syndrome, functional gastrointestinal disorders and gastrointestinal dysmotility, such as that occurring in conjunction with other disease states, in critical care situations or as a result of treatment with pharmaceutical agents.

Abstract: The use of lipopeptides as inducers of NF-?B for the protection of mammals from the effects of apoptosis is described.

Abstract: The present invention describes compounds, processes for their preparation, pharmaceutical compositions containing them, and their use in therapy.

Abstract: The present invention relates to structural studies of dipeptidyl peptidase I (DPPI) proteins, modified dipeptidyl peptidase I (DPPI) proteins and DPPI co-complexes. Included in the present invention is a crystal of a dipeptidyl peptidase I (DPPI) and corresponding structural information obtained by X-ray crystallography from rat and human DPPI. In addition, this invention relates to methods for using structure co-ordinates of DDPI, mutants hereof and co-complexes, to design compounds that bind to the active site or accessory binding sites of DPPI and to design improved inhibitors of DPPI or homologues of the enzyme.

Abstract: Cell penetrating suppressor of cytokine signaling (CP-SOCS) molecules engineered to be resistant to intracellular degradation are discussed. Methods of treating diseases associated with cytokine signaling include one or more CP-SOCS degradation resistant molecules.

Abstract: The present invention is related to a composition capable of inhibiting the growth of tumoral cells of different histological origins and of activated endothelial cells. The components of said compositions are polypeptide fragments of the serralisins, corresponding to the C-terminal fragment, from the internal metionine trough the end of the molecule, which could be combined among them and optionally with the prodigiosins that potentiate the antitumoral effect of the composition. The prodigiosins in the composition could be at a concentration of 0.1-100 nM. The anti-proliferative action of this composition is mediated by apoptotic mechanism. It's “in vivo” administration has antitumoral, antiangiogenic and protective effect against malignant tumors.

Abstract: This document provides to methods and materials related to apoptosis. For example, methods and materials for modulating apoptosis are provided. In addition, methods and materials for treating a mammal having an apoptosis-associated condition are provided.

Abstract: The use of lipopeptides as inducers of NF-?B for the protection of mammals from the effects of apoptosis is described.

Abstract: The C-terminal domain of focal adhesion kinase (FAK-CD) was isolated using a Baculoviral system. Using phage display techniques, a phage encoding a 12 amino-acid peptide (peptide 35) and AV3 that binds to FAK-CD were identified. The peptides were also conjugated to TAT-FITC to produce a fluorescently labeled chimeric molecule capable of penetrating cell membranes. Contacting various breast cancer cell lines with these molecule caused detachment, rounding, apoptosis and cell death. These effects were not observed in normal (non-cancerous) breast cells.

Abstract: Smac mimetics that inhibit IAPs.

Abstract: Provided is an agent which is useful for diagnosis, prevention, and treatment of various diseases induced by an oxidative stress. Disclosed are secreted eIF5A protein and a pharmaceutical containing the same.

Abstract: An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

Abstract: This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or immune cell growth. The invention provides methods of inhibiting interactions between MUC1 and BH3-containing proapoptotic proteins, methods of inhibiting MUC1 expression, and methods of promoting apoptosis. Also provided are screening methods for compounds that inhibit interactions between MUC1 and BH3-containing proapoptotic proteins and pharmaceutical compositions of the same.

Abstract: The present invention provides a means of selectively killing epithelial cell carcinomas by administering a CXCR4-specific sequence of the Gp120 protein or Nef proteins or the proteins themselves (the modulators) such as that found in strains HIV-1, HIV-2, SIV, or FIV CXCR4-specific Gp 120 sequences or Nef proteins or sequences may be delivered to the mucosa or systemically. The mucosal means of application include oral, intranasal, ocular, intravaginal, rectal, and/or intraurethral administration in liquid or particulate form.

Abstract: Enamel matrix, enamel matrix derivatives and/or enamel matrix proteins or peptides may be used as therapeutic or prophylactic agents for inducing programmed cell death (apoptosis), in particular in the treatment or prevention of cancer or malignant or benign neoplasms.

Abstract: The present invention provides the amino acid of a protein that inhibits cellular apoptosis, herein termed the Survivin protein and nucleic acid molecules that encode Survivin. Based on this disclosure, the present invention provides isolated Survivin protein, isolated Survivin encoding nucleic acid molecules, methods of isolating other members of the Survivin family of proteins, methods for identifying agents that block Survivin mediated inhibition of cellular apoptosis, methods of using agents that block Survivin mediated inhibition or Survivin expression to modulate biological and pathological processes, and methods of assaying Survivin activity.

Abstract: The present invention provides fusion peptides having GLP-1 activity and enhanced stability in vivo, in particular resistancy to dipeptidyl peptidase IV. The fusion peptide comprises as component (I) N-terminally a GLP-1(7-35, 7-36 or 7-37) sequence and as component (II) C-terminally a peptide sequence of at least 9 amino acids or a functional fragment, variant or derivative thereof. Component (II) is preferably a full or partial version of IP2 (intervening peptide 2). A preferred embodiment comprises the sequence GLP-1(7-35, 36 or 37)/IP2/GLP-1(7-35, 36 or 37) or GLP-2. The fusion peptide may be produced in engineered cells or synthetically and may be used for the preparation of a medicament for treating various diseases or disorders, e.g. diabetes type 1 or 2, apoptosis related diseases or neurodegenerative disorders.

Abstract: The present invention relates to a method of protecting cells against damage caused at least in part by apoptosis, comprising administering to subjects a therapeutic dose of leumorphin having cytoprotective activity, and a pharmaceutical composition comprising an effective amount of leumorphin having a cytoprotective activity.

Abstract: This invention provides methods and pharmaceutical compositions for regulating cell growth or inducing apoptosis in a cell, particularly a mammalian tumor cell. Specifically, the invention provides methods for inducing apoptosis in a tumor cell comprising contacting the tumor cell with a proteasome inhibitor and a thiazole antibiotic, particularly each in a suboptimal amount.

Abstract: The invention includes an isolated peptide comprising all or part of the amino acid sequence: EGKLSSNDTE GGLCKEFLHP SKVDLPR (SEQ ID NO: 1), wherein the peptide inhibits calcium channel activity. The peptides of the invention are useful for preventing or treating cancer.

Abstract: The present invention relates generally to a method of modulating tumor necrosis factor-mediated apoptosis and to agents useful for same. More particularly, the present invention contemplates a method of modulating tumor necrosis factor-mediated hepatocyte apoptosis by modulating an intracellular Bim and/or Bid-dependent signalling mechanism. The method of the present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterized by aberrant, unwanted or otherwise inappropriate tumor necrosis factor-mediated apoptosis. The present invention is further directed to methods for identifying and/or designing agents capable of modulating the subject Bim and/or Bid-dependent signalling mechanism.

Abstract: The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula (I), and G, X1, X2, R1, R2, R3, R4, R4?, R5, Ra, Rb, and Rc are as described herein.

Abstract: A method of inhibiting apoptosis in a cell includes administering to a cell an effective amount of a cell penetrating peptide (CPP), wherein the CPP consists of about 5 to about 41 amino acids and is substantially homologous to a portion of the C-terminal region of IFN?R2.

Abstract: Compositions for regenerating tissue and wound repair, among other applications, are described.

Abstract: The present invention relates to a composition for inhibiting gastrointestinal inflammation comprising an effective amount of Lactoacillus casei rhamnosus secreted factors 5 to 30K fraction.

Abstract: Disclosed herein are CPG15 and CPG15-2 compounds and inhibitors that act as agonists and antagonists of the insulin receptor and insulin-like growth factor receptors, and the use of such compositions for the treatment of insulin and insulin-like growth factor-related diseases.

Abstract: The invention is directed to a method of modulating paraptotic cell death in a cell by contacting the cell with an effective amount of a compound. selected from the group consisting of ceramide, Tumor Necrosis Factor (TNF), caspase-7, caspase-8, ?-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (RMPA), kainic acid and glutamic acid, wherein the effective amount of the compound induces paraptotic death of the cell. The invention further is directed to a method of inhibiting paraptotic cell death in a cell by contacting the cell with an effective amount of a compound selected from the group consisting of Alg-2-interacting protein 1 (AIP-1), Jun N-terminal kinase 1 (JNK1) neutralizing agent, Jun N-terminal kinase 2 (JNK2) neutralizing agent, TNF Receptor-Associated Factor 2 (TRAF2) neutralizing agent, ortho-phenanthroline and the JNK inhibitor SP 600125, wherein the effective amount of the compound inhibits paraptotic death of the cell.

Abstract: Provided is a method of using soluble CD14 or peptides derived therefrom for protecting cells from death, specifically from apoptotic cell death. Further provided are compositions including CD14 or CD14 peptides and methods for protecting cells, in particular lymphocytes, from apoptotic cell death. The compositions and methods are relevant, in particular, for the treatment of various immune deficiencies associated, for example, with cell transplantation procedures, autoimmune diseases and infectious diseases such as HIV.

Abstract: Processes for inhibiting apoptotic cell death and glycosaminoglycan release from injured cartilage is provided. Inhibition is accomplished using caspase inhibitors.

Abstract: Described herein are chemokine-binding domains of THAP-family polypeptides and pharmaceutical compositions which include a polypeptide comprising a chemokine-binding domain of a THAP-family polypeptide. Also disclosed are methods of binding chemokines, inhibiting the activity of chemokines, detecting chemokines, and reducing the symptoms associated with a chemokine mediated or influenced condition by contacting the chemokine with an agent that includes a polypeptide comprising a chemokine binding domain of a THAP-family polypeptide.

Abstract: Isolated histidyl-tRNA synthetase splice variant polynucleotides and polypeptides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Abstract: Compositions and methods for restoring killing of cancer cells are provided. Preferably, the compositions are administered to a subject in an effective amount to antagonize, inhibit, reduce, or block B7-H1 mediated signal transduction in cancer cells expressing B7-H1. It has been discovered that B7-H1 transmits an anti-apoptotic signal in cancer cells that increases the resistance of the cancer cells to CTL mediated cytolysis and to Fas induced cell death. It is believed that blocking the transmission of the anti-apoptotic signal by B7-H1 increases the susceptibility of the cancer cells to apoptosis and CTL cytolysis thereby enhancing the death of cancer cells. Preferred compounds or B7-H1 antagonists include antibodies that bind to B7-H1, B7-H1 receptors, or ligands of B7-H1 such as PD-I or B7-1.

Abstract: The present invention is based, at least in part, on the identification of a novel active site on BCL-2 family polypeptide such as BAX, which when bound by a compound, modifies the activity of the BCL-2 family polypeptide.

Abstract: Phosphorylated Apoptin is described. Apoptin is tumor-specifically phosphorylated and part of the Apoptin apoptotic pathway in tumor cells is elucidated. New therapeutic possibilities, for example, novel therapeutic compounds that can work alone or, sequentially to, or jointly with other known compounds. Also, the use of tumor-specifically phosphorylation of Apoptin for diagnostic purposes is described. Such a diagnostic purpose can, for example, be a method for detecting the presence of cancer cells or cells that are cancer prone or a method to identify a putative cancer inducing agent or a method for the in vitro treatment effect of Apoptin on tumor cells by testing the phosphorylation state of Apoptin. Even more, the invention provides possibilities to further elucidate the apoptotic pathway and to identify for example crucial mediators of phosphorylation in human tumor cells. Interfering with such a mediator could provide new anti-cancer therapies.

Abstract: The invention provides a method for determining sensitivity of a cell population to apoptosis induced by Smac mimetics as a single agent or in combination with other chemodrugs, which method comprises assaying for an epigenetic modification at the TNF? locus in the cell population as compared to the TNF? locus in a cell population not sensitive to apoptosis induced by Smac mimetics as a single agent or in combination with other chemodrugs, wherein the presence of the epigenetic modification indicates that the cell population is sensitive to apoptosis induced by Smac mimetics as a single agent or in combination with other chemodrugs.

Abstract: The invention provides compositions and method for delivering a therapeutic or diagnostic agent to a disease site in a mammal, the method comprising administering to the mammal a therapeutically or diagnostically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises the therapeutic or diagnostic agent coupled to a Procaspase 8 polypeptide and a pharmaceutically acceptable carrier.

Abstract: Novel polypeptides, designated Apo-2DcR, which are capable of binding Apo-2 ligand are provided. Compositions including Apo-2DcR chimeras, nucleic acid encoding Apo-2DcR, and antibodies to Apo-2DcR are also provided.

Abstract: Novel PYRIN-2, PYRIN-3, PYRIN-5, PYRIN-6, PYRIN-7, PYRIN-8, PYRIN-10, and PYRIN-11 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated PYRIN-2, PYRIN-3, PYRIN-5, PYRIN-6, PYRIN-7, PYRIN-8, PYRIN-10, and PYRIN-11 proteins, the invention further provides PYRIN-2, PYRIN-3, PYRIN-5, PYRIN-6, PYRIN-7, PYRIN-8, PYRIN-10, and PYRIN-11 fusion proteins, antigenic peptides and anti-PYRIN-2, -PYRIN-3, -PYRIN-5, -PYRIN-6, -PYRIN-7, -PYRIN-8, -PYRIN-10, and -PYRIN-11 antibodies. The invention also provides PYRIN-2, PYRIN-3, PYRIN-5, PYRIN-6, PYRIN-7, PYRIN-8, PYRIN-10, and PYRIN-11 nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a PYRIN-2, PYRIN-3, PYRIN-5, PYRIN-6, PYRIN-7, PYRIN-8, PYRIN-10, or PYRIN-11 gene has been introduced or disrupted.

Abstract: The present invention encompasses compositions and methods directed to preventing, inhibiting, or treating inflammation, alveolar remodeling, or cell death in lung which results from elevation of IL-18, IFN-?, or PKR where the methods of the present invention comprise administering an IL-18 inhibitor, an IL-18R? inhibitor, and IFN? inhibitor, a PKR inhibitor, and any combination thereof to an individual experiencing inflammation, alveolar remodeling, or cell death in lung. The present invention further encompasses a method of alleviating exacerbations of COPD frequently caused by viral infection by administering inflammation, alveolar remodeling, or cell death in lung to a patient with COPD at risk of developing a viral infection or who has acquired a viral infection.