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: Mullerian Inhibiting Substance analogues are disclosed which comprise one or more non-naturally occurring N-linked glycosylation sites, protease cleavage sites, and/or tags such as an epitope tag. Also disclosed are pharmaceutical compositions comprising such compositions and methods of using such compositions, for example in the treatment of conditions associated with uncontrolled growth of a tissue derived from a Mullerian duct, such as the condition endometriosis.

Abstract: Compositions containing epidithiodioxopiprazines and methods of their use are provided. Epidithiodioxopiprazines can be isolated from natural resources or synthesized de novo. Moreover, epidithiodioxopiprazines, including Verticillin A, are shown to effectively sensitize multiple types of tumor cells to TRAIL-induced apoptosis. In addition, epidithiodioxopiprazines, including Verticillin A, are shown to effectively overcome cancer cell resistance to existing drugs (i.e. Etoposide, Cisplatin, 5-FU and Doxorubicin). Therefore, compositions and methods are provided for use in sensitizing target cancer cells to death receptor- and other anticancer drugs-induced apoptosis. Methods of treating cancer in a subject in need thereof are also provided.

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: A method includes obtaining a biological sample from a subject that does not display a symptom of Painful Bladder Syndrome (PBS). The method also includes analyzing the biological sample for a mutated form of NAD(P)H dehydrogenase [quinone], also known as Quinone Oxidoreductase 1, abbreviated NQO1, or a mutation of a NQO1 gene. The method also includes determining a risk of PBS for the subject based on analyzing the biological sample. In some methods, the mutation determined to present an increased risk is a cytosine to thymine nucleotide substitution at a position that leads to a proline to serine amino acid substitution at amino acid position 187 to produce a protein NQO1P187S. Another method includes selecting a subject that has above normal risk of Painful Bladder Syndrome (PBS) or is expressing a symptom of PBS, and treating the subject with a therapeutically effective amount of an antioxidant.

Abstract: A pharmaceutical composition including, as an active ingredient, one of the following proteins (I) and (II): (I) an apoptosis inhibitor of macrophage; and (II) a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of the apoptosis inhibitor of macrophage and having homology to the amino acid sequence of the apoptosis inhibitor of macrophage, and has a function of inhibiting the differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes.

Abstract: Administration of compositions comprising cell-permeable caPCNA-derived peptides and their variants reduces the proliferation of cancer cells and also augments cytotoxic effects of chemotherapeutics. The compositions are effective in cells harboring mutations in DNA repair proteins.

Abstract: Disclosed herein is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I: or a prodrug, or a pharmaceutically acceptable salt, or labeled with a detectable label or an affinity tag thereof; wherein R1, R1a, R100, R100a, R2, R200, W, B, and W1 are defined herein. Also disclosed are methods of using compounds of Formula I to treat proliferative disorders such as cancer.

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: Methods for predicting negative consequences of a treatment of a patient with a therapy comprising determining the genetic status of the patient's tumor with respect to p53 by determining in a sample of body fluid or a tissue sample of the patient containing tumor cells or cell-free tumor DNA whether the whole p53 gene is present in native form or whether the p53 gene has one or more mutations. In further embodiments the patient is predicted to be a patient who will suffer negative consequences of a therapy interfering with the cell cycle if the whole p53 gene is present in native form and a patient who will suffer negative consequences of a therapy inducing p53 dependent apoptosis if the p53 gene has one or more mutations. Methods of treatment are also contemplated.

Abstract: The present invention provides materials and methods useful to treat various sGC?1-expressing cancers. Materials include peptides which interfere with sGC?1's pro-survival functions, thereby resulting in apoptosis of sGC?1-expressing cells. In addition, the present invention provides screening assays, diagnostic assays, methods to prognose, methods to treat, and kits.

Abstract: The present invention provides therapeutic and prophylactic compositions for use in treating and preventing disorders involved epithelial cell apoptosis, such as gastrointestinal disorders (e.g., inflammatory bowel disease, Crohn's disease or ulcerative colitis) in a subject, such as a human patient.

Abstract: The disclosure provides Apo-2 ligand variant polypeptides. Methods of making and chemically modifying Apo-2 ligand variant polypeptides are also provided. In addition, formulations of Apo-2 ligand variant polypeptides are provided. In addition, therapeutic methods for using Apo-2 ligand variant polypeptides are provided.

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: Proliferation of colorectal, gastric and esophageal cancer cells is inhibited by administering ST receptor ligand. The number of ST receptor molecules on the surface of a colorectal cell or metastasized colorectal cancer cell are increased by administering an ST receptor ligand such that ligand comes into contact with an ST receptor on the surface of the colorectal cell. Pharmaceutical compositions comprise sterile, pyrogen free ST receptor ligand and a pharmaceutically acceptable carrier or diluent. Metastasized colorectal cancer is treated or imaged by increasing the number of ST receptor molecules on the surface of a metastasized colorectal cancer cell and then administering a pharmaceutical composition containing components that target the ST receptor for delivery of a therapeutic agent or imaging agent. Methods of detecting metastasized colorectal cancer are disclosed. Methods of delivering active compounds to a colorectal cell in an individual are disclosed.

Abstract: Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.

Abstract: Agonists for TRAIL death receptors including polypeptides having a multimerizing, e.g. trimerizing, domain and a polypeptide sequence that binds to at least one of TRAIL death receptors TRAIL-R1 and TRAIL-R2. Agonists are described that do not bind to TRAIL decoy receptors. The multimerizing domain may be derived from human tetranectin. The agonists can induce apoptosis in pathogenic cells expressing a TRAIL death receptor. Pharmaceutical compositions are described for treating diseases associated with cells expressing DR4 and DR5, such as tumor cells. Methods for selecting polypeptides and preparing multimeric complexes.

Abstract: Conjugates of transferrin or transcobalamin with anti-viral agents are useful in the treatment of viral infections. Suitable anti-viral agents include apoptosis inducing compounds, compounds which inhibit the replication of the virus, a cytotoxic antibiotic, an alkylating agent, a plant toxin, and a bacterial mutant toxin. Transferrin or transcobalamin is preferably coupled to the anti-viral agent by means of glutaraldehyde.

Abstract: The HIV-1 accessory gene vpr encodes a conserved 96-amino acid protein that is necessary and sufficient for the HIV-1-induced block of cellular proliferation and induction of apoptosis. Expression of vpr in CD4.sup.+ lymphocytes results in G2 arrest, followed by apoptosis. ATR, as a cellular factor that mediates Vpr-induced cell cycle arrest, is required for activation of the Breast Cancer-Associated Protein-1 (BRCA1). In addition, the Growth Arrest and DNA Damage protein (GADD45) is upregulated by Vpr in an ATR-dependent manner. Posttranscriptional silencing of either ATR or GADD45 leads to nearly complete suppression of the pro-apoptotic and/or cell cycle arrest effect of Vpr.

Abstract: The invention relates to selective new caspase-2 inhibitors that recognize caspase-2 and prevent and block its activity based on the following backbone: 2-Quinolinylcarbonyl-L-Valinyl-L-Aspartyl (methyl ester)-L-Valinyl-L-Alanyl-L-Aspartyl (methyl ester) 2,6-difluorophenyl ester SEQ ID NO:1) and derivatives thereof, SEQ ID NO:1 corresponding to formulae Ia or Ib. Application of the inhibitors for preventing and treating diseases involving caspase-2.

Abstract: Anti-DR5 antibody agonists, combined with apoptosis-inducing agents, synergistically induce apoptosis in cancer cells.

Abstract: The present invention concerns improved osteoinductive materials comprising matrix materials and morphogenetic proteins, wherein depending on the subject matter the proteins may be dimeric or monomeric proteins. The osteoinductive materials according to the present invention have improved properties. The invention further concerns methods for producing the respective improved osteoinductive materials.

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 an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases, for example, an interaction of the X chromosome linked IAP (XIAP) and caspase-3, caspase-7 or caspase-9, wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a caspase such as caspase-3 or caspase-7 or a pro-caspase such as pro-caspase-9, or that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP. The invention further provides methods of reducing the severity of a pathologic condition in an individual by administering to the individual an agent that alters the caspase inhibitory activity of an IAP.

Abstract: Smac mimetics that inhibit IAPs.

Abstract: Pharmaceutical compounds, pharmaceutical compositions and methods of treatment are disclosed, wherein a compound comprises a targeting moiety which, in free form, binds a cell receptor with a dissociation constant Kd of less than about 10?7 M, and a pharmaceutically active moiety, wherein the targeting moiety is other than an oligopeptide, a polypeptide, a peptidomimetic, a protein or a protein domain, and wherein the targeting moiety and the pharmaceutically active moiety are covalently attached. In some aspects, the targeting moiety binds a sigma-2 receptor with high affinity and high specificity, and the pharmaceutically active moiety is a pro-apoptotic peptide moiety. Methods of cancer treatment are disclosed comprising administering a disclosed pharmaceutical compound to a subject in need of thereof. The treatments selectively induce apoptosis in cancer cells. These methods can further comprise co-administration of radiation therapy and/or an additional chemotherapeutic agent.

Abstract: The present invention is directed to compositions of matter useful for the enhancement of apoptosis in mammals and to methods of using those compositions of matter for the same.

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

Abstract: The present invention relates generally to the mitochondrial protein, voltage-dependent anion channel (VDAC)5 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 instant invention provides a method of treating an animal suffering a disease characterized by excessive apoptosis by administering a therapeutically effective amount of at least one serine protease inhibitor and thereafter monitoring a decrease in apoptosis. The inhibitor of the invention includes ?1-antitrypsin or an ?1-antitrypsin-like agent, including, but not limited to oxidation-resistant variants of ?1-antitrypsin, and peptoids with antitrypsin activity. The diseases treatable by the invention include cancer, autoimmune disease, sepsis neurodegenerative disease, myocardial infarction, stroke, ischemia-reperfusion injury, toxin induced liver injury and AIDS. The method of the invention is also suitable for the prevention or amelioration of diseases characterized by excessive apoptosis.

Abstract: Methods and compositions for improving immune system function are provided. These methods find particular use in improving immune system function in individuals with a condition in which naïve lymphocytes comprise elevated amounts of DNA double strand breaks (DSB), for example, individuals with Rheumatoid Arthritis, individuals that have received a bone marrow transplant, or elderly individuals, e.g. individuals that are 50 or more years old. Also provided are methods and compositions for screening for novel compounds that will improve immune system function in such individuals.

Abstract: The present invention concerns a composition for potentiating formation of DISC (Death Inducing Signaling Complex) macro-complex and for inducing apoptotic signal mediated by death receptors in tumour cells comprising a therapeutically effective amount of an active agent selected among a hypocalcemia-inducing agent, a calcium channel inhibitor and a calcium chelator in association with a therapeutically effective amount of an anticancer agent inducing an apoptotic signal via death receptors Fas, TNF-R1, DR4 and/or DR5.

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 invention provides compositions and methods 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 an albumin binding peptide and a pharmaceutically acceptable carrier.

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 to a fusion protein comprising a protein transduction domain capable of introducing the fusion protein into a mammalian cell and an anti-apoptotic protein comprising the amino acid of the sequence of SEQ ID NO:1 or an anti-apoptotically active variant or fragment thereof. The invention also relates to a pharmaceutical composition comprising such a fusion protein, in particular for blocking apoptosis in a patient in need thereof. The invention also provides a polynucleotide encoding such a fusion protein, an expression vector comprising the polynucleotide and a host cell comprising the expression vector. In a further aspect, the invention relates to the use of any of theses materials for the preparation of a medicament for blocking apoptosis in a patient in need thereof.

Abstract: A purified polypeptide includes about 5 to about 80 amino acids and includes an amino acid sequence corresponding to a portion of SEQ ID NO:1. The polypeptide inhibiting binding of Bcl-2 to IP3 receptors of cells that express IP3R and Bcl-2.

Abstract: The present invention refers to protein kinase inhibitors and more specifically to inhibitors of the protein kinase c-Jun amino terminal kinase. Additionally, the present invention provides JNK inhibitor sequences, chimeric peptides, nucleic acids encoding same as well as pharmaceutical compositions for treating pathophysiologies associated with JNK signaling.

Abstract: Smac mimetics that inhibit IAPs.

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: A desired physiological state can be induced by altering the amount of gene products in target cells of a subject. The target cells are treated with at least one compound designed to reduce expression of at least one first gene by RNAi, and with at least one compound designed to increase expression from at least one second gene. The reduced expression of the first gene and the increased expression from the second gene in the target cells induces the desired physiological state in the subject. By altering target cell gene expression in this way, conditions such as angiogenesis or tumor growth and metastasis can be inhibited.

Abstract: Nitric Oxide (NO) acts as double-edged sword, which induces and prevents cell death, depending on various factors. The mechanism for the NO regulation of cells is not fully understood. The present invention provides experiment design methods and therapy design methods leveraging viable hypothesis supported by current research findings. This invention determines the effects of NO by controlling the majority parameters such as the steady-state concentration of NO, duration of NO exposure and the local level of oxygen. The experiment designs are structured to improve understanding of NO regulation of cells, and further can be directly adapted for therapy design. The invention directs these experiment design and therapy design methods to the study and treatment of cancer. In an application, the effects of exogenous NO on inducible Nitric Oxide Synthase (iNOS) expression and signal transduction in ovarian cancer is applied to drug discovery and therapy design for ovarian and other cancers.

Abstract: The invention provides novel compounds that are inhibitors of IAPs having the general formula: wherein X1, X2, X3, Y, A, R1, R2, R3, R4, R4?, R5, R5?, R6 and R6? are as described herein. The compouds of the invention may be used to induce apoptosis in cells (or sensitise cells to apoptosis) in which IAPs are overexpressed or otherwise implicated in resistance to normal apoptotic processes. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment cancers.

Abstract: Described are mitochondria-targeted anti-tumor agents, death receptor agonists, autophagy inhibitors, and NF-?B signaling pathway inhibitors, and methods of making and using the same for the treatment of disorders associated with unwanted cell proliferation.

Abstract: The present invention relates to novel synthetic or natural peptides for use in treating viral or parasitic infections or in the treatment of tumors. The peptides of the present invention are less than 30 amino acids in size, preferably less than 20 amino acids, in particular 15 to 20 amino acids, and in vitro the peptides specifically bind a type 2A protein phosphatase holoenzyme or one of its subunits. The invention also relates to a method for identifying said peptides, and to their uses.

Abstract: In one aspect, the invention provides covalent conjugates between artemisinin-related endoperoxides and iron-carrying proteins. In some embodiments, the covalent conjugates comprise artelinate and holotransferrin. In another aspect, the invention provides methods for administering the covalent conjugates of the invention to treat cancer and infections by pathogens that bind iron-carrying proteins.

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: Methods are provided for inhibiting cell death or inflammation in a mammal concurrent with or after the onset of a condition expected to lead to cell death or inflammation. The methods each include the step of administering to a mammal a Bcl protein in an amount sufficient to inhibit cell death or inflammation in the mammal. Methods are also provided for identifying a Bcl protein that inhibits cell death or inflammation when administered to a mammal concurrent with or after the onset of a condition expected to lead to cell death or inflammation.

Abstract: The invention relates to methods for identifying genes involved in TRAIL-induced apoptosis, to inhibitors of the expression of genes inducing resistance of cells to TRAIL-induced apoptosis and to activators of the expression of a gene sensitizing cells to TRAIL-induced apoptosis. The invention also relates to methods for sensitizing cells to TRAIL-induced apoptosis, methods for treating hyperproliferative diseases, methods for determining the responsiveness of a subject suffering from a hyperproliferative disease to TRAIL, to pharmaceutical compositions comprising products capable of sensitizing cells to TRAIL-induced apoptosis, and to methods for determining the prognosis of a subject suffering from a hyperproliferative disease.

Abstract: Fusion proteins which act on the TWEAK and TRAIL signaling axes are provided. The proteins are useful in the treatment or amelioration of autoimmune diseases, particularly multiple sclerosis, as well as other diseases such as alloimmune diseases and cancer.