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: Provided are antibodies specifically binding to the epidermal growth factor receptor (EGFR) which are effective for the treatment of EGFR-mediated cancers.

Abstract: Methods to treat certain types of cancer with cyclophilin inhibitors.

Abstract: Peptides, compositions and methods for modulating apoptosis, useful for treating diseases or disorders characterized by dysregulated apoptosis, such as cancer or neurodegenerative diseases. Screening methods for identifying agents that mediate apoptosis by regulating Atg12 binding to Bcl-2 family members.

Abstract: The present invention relates to kinase inhibiting compositions and uses thereof. The invention further provides isolated kinase inhibiting peptides and uses thereof for inhibiting hyperplasia, for inhibiting the growth of neoplasms, and for inducing programmed cell death in a cell population.

Abstract: The present invention relates to compositions and methods relating to an interleukin18-inducible cytokine termed tumor necrosis factor-alpha inducing factor (TAIF) or interleukin-32 (IL-32). In particular, the present invention provides compositions and methods for treating autoimmune diseases and cancer, in part by regulation of tumor necrosis factor-alpha expression.

Abstract: Methods and compositions are provided for the persistent modification of cell membranes with exogenous proteins so as to alter the function of the cell to achieve effects similar to those of gene therapy, without the introduction of exogenous DNA. DNA sequences, the proteins and polypeptides embodying these sequences are disclosed for modulating the immune system. The modulations include down-regulation, up-regulation and apoptosis.

Abstract: There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

Abstract: An autophagy-inducing compound comprises an autophagy-inducing peptide comprising beclin-1 residues 269-283 and a heterologous moiety that promotes therapeutic stability or delivery of the compound. The compound may be used to induce autophagy and in assays with beclin-1 binding partners.

Abstract: A method of treatment of inflamed, pre-cancerous or cancerous tissue or polyps in a mammalian subject is disclosed. The treatment involves administration of a composition of at least one peptide agonist of a guanylate cyclase receptor and/or other small molecules that enhance intracellular production of cGMP. The at least one peptide agonist of a guanylate cyclase receptor may be administered either alone or in combination with an inhibitor of cGMP-dependent phosphodiesterase. The inhibitor may be a small molecule, peptide, protein or other compound that inhibits the degradation of cGMP. Without requiring a particular mechanism of action, this treatment may restore a healthy balance between proliferation and apoptosis in the subject's population of epithelial cells, and also suppress carcinogenesis.

Abstract: A purified paracrine factor of a mesenchymal stem cell, such as a Secreted frizzled related protein (Sfrp) is useful to reduce cell death and/or tissue injury associated with ischemic conditions.

Abstract: Provided is a method of determining the level of resistance or sensitivity of cancer stem cells to a death receptor agonist. The method includes detecting the level of IAP in one or more DR5/DDX3/IAP complexes in or from the cancer stem cells. Also provided is a method of killing cancer stem cells in a subject and a method of reducing the risk of cancer recurrence in a subject.

Abstract: This invention relates generally to methods and agents for modulating adiposity-related conditions. More particularly, the present invention relates to the use of TRAIL death receptor agonists, including nucleic acids such as TRAIL polynucleotides, peptides and polypeptides including TRAIL polypeptides, TRAIL DR agonist antigen-binding molecules, TRAIL DR peptide agonists as well as small molecule TRAIL DR agonists in compositions and methods for treating or preventing adiposity-related conditions such as obesity, diabetes mellitus and metabolic syndrome.

Abstract: A method of treating a disease characterized by aberrant cell migration and/or invasion includes administering to a subject an effective amount of the peptide of SEQ ID NO:3, an ?6 polypeptide, or an isolated polypeptide consisting essentially of the Link region of human CD44 as indicated in FIG. 17 to modulate a FAK signal transduction pathway for a sufficient period of time to treat the disease. A method of diagnosing a condition characterized by aberrant cell migration and/or invasion includes measuring the effect of these polypeptides on FAK signal transduction activity; wherein a change in FAK signal transduction activity is indicative of said aberrant cell migration or invasion. A method of diagnosing a condition characterized by aberrant cell migration and/or invasion includes imaging FAK signal transduction activity in the presence of these polypeptides.

Abstract: A method of stimulating neuronal growth or repair comprising exposing a target neuron or neuronal area to a solution of the metallothionein isoform MT-IIA.

Abstract: The present invention relates to pharmaceutical combinations comprising dual Angiopoietin-2/DII4 binders and anti-VEGF-R agents for use in treating diseases like cancer and ocular diseases.

Abstract: The present invention relates to pharmaceutical combinations comprising dual Angiopoietin-2/Dll4 binders and anti-VEGF agents for use in treating diseases like cancer and ocular diseases.

Abstract: Disclosed herein are compounds that inhibit Hsp90 interactions with IAP proteins, such as Survivin, XIAP, cIAP1, or cIAP2, and methods for identifying and using such compounds.

Abstract: The invention relates to pharmaceutical compositions comprising leukotoxin, a chemotherapeutic agent and a pharmaceutically acceptable carrier, including methods to treat cancer, and methods to induce apoptosis.

Abstract: A SMAC mimetic and pharmaceutical compositions thereof and methods of use.

Abstract: An autophagy-inducing compound comprises an autophagy-inducing peptide comprising beclin-1 residues 269-283 and a heterologous moiety that promotes therapeutic stability or delivery of the compound. The compound may be used to induce autophagy and in assays with beclin-1 binding partners.

Abstract: The invention provides cell-permeable peptides that bind to JNK proteins and inhibit JNK-mediated effects in JNK-expressing cells.

Abstract: We describe preparation of compounds of an AT1 receptor antagonist(s) and Angiotensin (1-7), for example, Angiotensin-(1-7) losartanate and analogues thereof, and/or mixtures of these systems, pharmaceutical compositions thereof and use of their derivative products. Cyclodextrins and derivatives thereof may be used for the micro-encapsulation of compounds, for example, Angiotensin (1-7) losartanate, liposomes and biodegradable polymers and/or mixtures of these systems and/or derivative products for the obtainment of nano- or microparticles as controlled or sustained release devices of Ang-(1-7) losartanate and analogues and/or mixtures thereof. The compounds may be used as agents for treating or preventing hypertension, cardiovascular diseases, heart hypertrophy, heart failure, coronary diseases, such as angina pectoris, endothelial disorder or endothelial lesions, as a consequence, for example, of atherosclerosis processes or in association with diabetes mellitus.

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

Abstract: The invention provides tight junction protein modulators, compositions comprising the same, and uses thereof. In particular, the invention provides tight junction protein modulators that modulate the second extracellular loop of tight junction proteins, such as occludin or claudin.

Abstract: Pharmaceutical compositions and methods for sensitizing multi-drug resistant cancer or radiation resistant cancer cells to chemotherapeutic agents are provided. Compositions include ligands of hyaluronan receptors, including glycosaminoglycans such as hyaluronan oligomers and derivatives of these oligomers, hyaluronan binding proteins, antibodies specific for hyaluronan receptors, hyaluronan mimetics, inhibitors of hyaluronan synthesis, and stimulators of hyaluronan degradation.

Abstract: The present invention relates generally to the mitochondrial protein, voltage-dependent anion channel (VDAC), polynucleotides encoding same and variants thereof, as well as peptide fragments, peptide derivatives and analogs. In particular, the present invention is directed to VDAC1 and specific amino acid and polynucleotide sequences thereof useful in inducing or regulating apoptosis and to pharmaceutical compositions comprising same useful in the treatment of diseases associated with aberrant apoptosis.

Abstract: The invention provides methods of making and using compositions comprising a polymer shell designed to deliver polypeptides to selected environments. In embodiments of the invention, different environmental conditions are harnessed to allow the selective degradation of the polymer shell and the consequential release of one or polypeptides encapsulated therein. In illustrative embodiments, polymer components of the shell are interconnected by disulfide-containing crosslinker moieties, linkages which maintain the integrity of the polymer shell under certain environmental conditions including those occuring outside of cells, but degrade in an intracellular environment.

Abstract: The invention provides small molecule mimics of the Smac peptide that are dimer-like or trimer-like compounds having two or three amide-containing domains connected by a linker. These compounds are useful to promote apoptosis. The invention includes pharmaceutical compositions comprising such compounds and methods to use them to treat conditions including cancer and autoimmune disorders.

Abstract: The present invention provides a method to identify a test compounds capability to modulate p75.sup.NTR induced apoptosis, said method comprising: i. Transfecting a suspension of eukaryotic cells with a vector encoding SEQ ID No.4 OR SEQ ID No.6), ii. Contacting said cells with the compound to be tested, and iii. Determine the apoptotic response in said cells, wherein an alteration in apoptotic response in the presence of said test compound compared to the apoptotic response in the absence of the test compound is an indication of the ability of the test compound to modulate p75.sup.NTR induced apoptosis.

Abstract: The invention relates to polypeptides comprising an amino acid sequence which is an analogue of pramlintide, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Abstract: The present invention relates to Death Receptor-6 (DR6) proteins which are members of the tumor necrosis factor (TNF) receptor family, and have now been shown to be important for regulating apoptosis in cells of the nervous system. In addition, it has been discovered that p75 is a ligand for DR6. As a result, this invention relates to methods for inhibiting the interaction of DR6 and p75 using DR6 and/or p75 antagonists. In addition, the methods described herein include methods of promoting survival of cells of the nervous system using DR6 antagonists, optionally in combination with p75 antagonists, and methods of treating neurodegenerative conditions by the administration of a DR6 antagonists, optionally in combination with a p75 antagonist.

Abstract: The NSAID, sulindac and/or its metabolites and derivatives, in combination with hydrogen peroxide or another oxidizing agent, such as arsenic trioxide that generates reactive oxygen species (ROS), significantly enhances the killing of cancer cells. This effect occurs at concentrations of each compound that individually have little or no activity directed against cancer cells. A skin cream has been developed and used to treat skin cancer and precancerous skin growths that effectively removes the lesions with no effect on surrounding normal skin.

Abstract: The present invention discloses a novel antitumour agent which provides an antitumour activity based on metabolites with reduced side effects. Moreover, the antitumour agent is prepared starting with a highly safe bacterium used in food production, which is a probiotic lactic acid bacterium.

Abstract: This invention provides compositions and method of diminishing or inhibiting autophagy by administering a FLIP protein that binds to Atg3, interfering with the formation of the LC3-Atg4-Atg7-Atg3 conjugation complex necessary for autophagy induction. This invention also provides FLIP peptide fragments that promote or induce autophagy by interfering with the activity of FLIP.

Abstract: The invention provides small molecule mimics of the Smac peptide that are dimer- or dimer-like compounds having two amide-containing domains connected by a linker. These compounds are useful to promote apoptosis. The invention includes pharmaceutical compositions comprising such compounds and methods to use them to treat conditions including cancer and autoimmune disorders.

Abstract: The present invention is directed to compositions and methods for the treatment of retinoblastoma and neuroectodermal derived tumors, such as primitive neuroectodermal tumors (PNET) and neuroblastoma. In particular, the present invention is directed to the use of 4F-benzoyl-TN14003 peptide or analogs or derivatives thereof for treating neuroblastoma and retinoblastoma.

Abstract: A peptide comprising the amino acid sequence, X1X2RX3DX4X5X6X7 is provided, as well as a biomaterial comprising the peptide for use to treat conditions resulting from cell death or apoptosis.

Abstract: The invention related to chimeric peptides including a penetrating peptide and a binding domain of PP2A catalytic subunit to caspase-9 which have pro-apoptotic activity. These chimeric peptides may be used for the treatment of hyperproliferative disorders.

Abstract: Compositions and methods for stimulating an immune response against cells that express survivin are provided. The method is suitable for prophylaxis and/or therapy of autoimmune disorders. The method involves administering to an individual a composition that contains a survivin peptide mimic that has a cysteine to methionine alteration at amino acid position 57 of wild type survivin. Fragments of the peptides can also be used.

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 is directed towards an isomer, an enantiomer, a diastereoisomer, or a tautomer of a pyrrolidine compound represented by Formula I: in which the substituents R1, R1a, R2, R2a, R3, A and Q are defined herein; or a prodrug, or a salt thereof, and which bind to IAP BIR domains. In particular, the compounds are useful in treating proliferative disorders such as cancer.

Abstract: The present invention provides novel, modified pokeweed antiviral proteins, nucleic acids that encode the proteins, conjugates that incorporate the proteins, and methods to make and use the proteins. The present invention also provides methods to administer the conjugates to animals, for the purpose of directing toxin to particular cells.

Abstract: The invention relates to fragments of the DAXX and FADD proteins that inhibit cell apoptosis, in particular cell apoptosis mediated by the Fas receptor. The invention also relates to derivatives of said anti-apoptotic fragments, conjugates comprising said fragments, pharmaceutical compositions comprising said fragments, and to the medical applications of said fragments, derivatives, conjugates, and pharmaceutical compositions thereof in the treatment or prevention of diseases and conditions associated with apoptosis.

Abstract: Therapeutic compositions comprising at least one 8-substituted-dibenzylbutyrolactone lignan, preferably a lignan is selected from the group of nortrachelogenin, diasteromeric forms of nortrachelogenin, isomeric forms of nortrachelogenin and combinations thereof as well as 8-methylmatairesinol and 8-methyldimethylmatairesinol, for use in a method of treating cancer or a similar condition wherein the growth factor signaling pathway of a mammal is deregulated. The invention also provides therapeutic pharmaceutical combinations comprising a hydroxy-dibenzylbutyrolactone lignan and at least one TRAIL receptor agonist. The hydroxy-dibenzylbutyrolactone lignans and a TRAIL receptor agonist can be used as a combined preparation for administration to a patient simultaneously, separately or spaced out over a period of time in treating cancer.

Abstract: The invention provides method of treating cancers that express MUC1 by the administration of PI3-K inhibitors in combination with MUC1-directed cancer therapies. The PI3-K inhibition may advantageously be combined with peptides that inhibit MUC1 oligomerization, or further with other standard anticancer therapies such as chemo-, radio- and surgical therapies.

Abstract: This invention provides an inducer of apoptosis in cancer cells comprising a fragment of the REIC/Dkk-3 gene and a cancer therapeutic agent comprising the same. This invention also provides a polynucleotide fragment encoding the REIC/Dkk-3 protein (a) or (b), which encodes a polypeptide having apoptosis activity: (a) a polynucleotide encoding a polypeptide comprising an amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2; or (b) a polynucleotide encoding a polypeptide comprising an amino acid sequence derived from the amino acid sequence of amino acid 1 to any of amino acids 39 to 78 of the amino acid sequence of the REIC/Dkk-3 protein as shown in SEQ ID NO: 2 by substitution, deletion, or addition of 1 or several amino acids and having apoptosis activity.

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: A therapeutic agent for treating an infectious or inflammatory disease, a pharmaceutical composition for treating an infectious or inflammatory disease, and a method of using a pharmaceutical composition are provided. The pharmaceutical composition includes a peptide ligand that binds with CXCR2 as an active component. The active component can be useful in preventing and treating infectious and/or inflammatory diseases, including sepsis and septic shock by promoting the removal of bacteria by phagocytosis, suppressing an inflammatory response, and suppressing the apoptosis of immune cells.

Abstract: This document provides methods and materials involved in modulating a cell's ability to be resistant to apoptosis. For example, methods and materials for exposing cells to KLK6 polypeptides, or increased KLK6 polypeptide activity, to promote resistance to apoptosis are provided. In addition, methods and materials for reducing the ability of KLK6 polypeptides to promote resistance to apoptosis are provided.