Abstract: The invention provides methods for determining a prognosis for survival for a cancer patient. One method involves (a) measuring a level of a TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) comparing the level of TUCAN in the sample to a reference level of TUCAN, wherein a low level of TUCAN in the sample correlates with increased survival of the patient. Another method involves (a) measuring a level of TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) classifying the patient as belonging to either a first or second group of patients, wherein the first group of patients having low levels of TUCAN is classified as having an increased likelihood of survival compared to the second group of patients having high levels of TUCAN.

Abstract: An assay for determining compounds that inhibit activity of a BCl-2 protein, or affect conversion of Bcl-2 from an antiapoptotic to a proapoptotic form are described. In addition, compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified.

Abstract: Disclosed herein are Vaccinia H1-related (VHR) protein tyrosine phosphatase (PTP) inhibitors that provide a method for treating cancer.

Abstract: Methods of using apogossypol and its derivatives for treating inflammation is disclosed. Also, there is described a group of compounds having structure A, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof are provided: wherein each R is independently selected from the group consisting of H, C(O)X, C(O)NHX, NH(CO)X, SO2NHX, and NHSO2X, wherein X is selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, an alkylaryl, and a heterocycle. Compounds of group A may be used for treating various diseases or disorders, such as cancer.

Abstract: A novel human member of the Bcl-2 family Bcl-B has been identified, which is closest in amino-acid sequence homology to the Boo (Diva) protein. The Bcl-B protein is widely expressed in adult human tissues. The Bcl-B protein modulates apoptosis. Bcl-B also binds Bcl-2, BCI-XL, and Bax but not Bak. Bcl-B displays a unique pattern of selectivity for binding and regulating the function of other members of the Bcl-2 family.

Abstract: The present invention provides a conjugate which contains a therapeutic moiety linked to a homing molecule that selectively homes to tumor blood vessels and tumor cells and that specifically binds the receptor bound by peptide KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK (SEQ ID NO: 9). Methods of directing a conjugate of the invention to tumor blood vessels and tumor cells and of using a conjugate to treat cancer also are provided.

Abstract: The present invention provides a method of providing acute neuroprotection by inducing the erythropoietin (EPO) signaling pathway in neuronal cells close to or subsequent to the time of excitatory insult; and inducing an insulin-like growth factor (IGF) signaling pathway in the neuronal cells close to or subsequent to the time of excitatory insult, thereby producing a synergistic acute neuroprotective effect in the neuronal cells. The invention also provides a method of preventing or reducing the severity of a neurologic condition in a subject by administering to the subject EPO or an active fragment or analog thereof at a dose of at most 2000 U/kg; and administering to the subject an IGF or an active fragment or analog thereof, thereby providing neuroprotection and preventing or reducing the severity of the neurologic condition.

Abstract: We have identified ZNF206, a novel repressor of human embryonic stem cell (hESC) differentiation. Repressing extra-embryonic endoderm development preserves the pluripotent state of human embryonic stem cells, and, conversely downregulating expression of ZNF206 in hESCs causes them to upregulate the expression of genes associated with the extra-embryonic endodermal lineage, down-regulate genes associated with the pluripotent state, and may lead to the further emergence of genes associated with even more differentiated lineages and phenotypes.

Abstract: This invention relates to Applicant's discovery that Metabolic Syndrome, a cluster of disorders stemming from a resistance to insulin, contributes directly to dementia, particularly Alzheimer's disease. Applicant's invention includes a screening method to determine susceptibility and diagnosis of dementia based on the risk factors for Metabolic Syndrome. Applicant's invention further includes methods for the prevention or treatment of dementia and other neurological conditions based on (1) minimizing insulin resistance, thereby preventing excess biosynthesis of insulin; (2) modulating the activity of IDE such that insulin competes less efficiently with ?-amyloid protein for the IDE; and (3) blocking the consequences of NMDA receptor activation, such as by minimizing the generation of NO and other harmful free radicals.

Abstract: Compositions and methods are provided that are based on a discovery that a combination of three compounds, doxycycline, selenium, and zinc, retards physiological age-related changes (for example cardiac aging and the decline in exercise capacity) and can also prolong survival.

Abstract: The invention provides a method of identifying an effective compound that modulates the binding of Humanin to Bax or Bid. The invention also provides a method of identifying an effective compound that modulates an activity of Bax or Bid. In addition, the invention provides a method of identifying a Humanin-like compound that binds to Bax or Bid or modulates an activity of Bax or Bid, or inhibits the apoptotic activity of Bax or Bid. The invention further provides an isolated polypeptide containing a mitochondrial-derived form of Humanin (SEQ ID NO:3) or a functional fragment thereof where the fragment contains the methionine at position 16 of SEQ ID NO:3.

Abstract: In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPs) and/or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and/or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and/or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and/or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein. Also provided are compositions and methods for targeting the destruction of selected polypeptides in eukaryotic cells based on the ubiquitin-independent mechanism by which ornithine decarboxylase is degraded by the 26S proteasome.

Abstract: The present invention relates to novel methods for identifying antiviral agents which selectively interfere with viral proteins that cause the unique infectivity activity of the SARS-coronavirus in comparison to other non-SARS strains of coronavirus. In particular, the present invention relates to screening assays that identify agents which selectively inhibit cyclic-AMP dependent protein kinase activity of the SARS-coronavirus ORF3. The present invention also relates to screening assays that identify agents which selectively inhibit the interaction between SARS-coronavirus cyclic-AMP dependent protein kinase and a calcium dependent targeting molecule. Therefore the agents identified using the assays of the invention may have utility as antiviral agents. The present invention also relates to treatments for sever acute respiratory syndrome caused by a coronavirus, and particularly to treatments that affect the infectivity activity of the SARS-coronavirus.

Abstract: Compounds that bind to Bfl-1 as well as conjugates of such compounds are provided. Various embodiments additionally provide methods of using such compounds to identify additional anti-apoptotic Bfl-1 binding compounds. Methods of using such compounds to increase apoptosis in a cell are also provided.

Abstract: The present invention provides a variety of isolated peptides and peptidomimetics, which can be useful, for example, in constructing the conjugates of the invention or, where the peptide itself has biological activity, in unconjugated form as a therapeutic for treating any of a variety of cardiovascular diseases as described below. Thus, the present invention provides an isolated peptide or peptidomimetic which has a length of less than 60 residues and includes the amino acid sequence CRPPR (SEQ ID NO: 1) or a peptidomimetic thereof. The invention further provides an isolated peptide or peptidomimetic which has a length of less than 60 residues and includes the amino acid sequence CARPAR (SEQ ID NO: 5) or a peptidomimetic thereof, or amino acid sequence CPKRPR (SEQ ID NO: 6) or a peptidomimetic thereof.

Abstract: Disclosed herein are tissue-nonspecific alkaline phosphatase (TNAP) activators and uses thereof for promoting bone mineral deposition.

Abstract: There are provided methods of inhibiting growth and metastasis of melanoma, methods of sensitizing melanoma cells to apoptosis, and methods of treating a subject having melanoma using acetyl isogambogic acid, celastrol, or a derivative thereof. There are further provided derivatives of celastrol and compositions comprising acetyl isogambogic acid, celastrol, or a derivative thereof.

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: Neurite outgrowth-promoting prostaglandins (NEPPs) and other electrophilic compounds bind to Keap1, a negative regulator of the transcription factor Nrf2, and prevent Keap1-mediated inactivation of Nrf2 and, thus, enhance Nrf2 translocation into the nucleus of neuronal cells. Therefore, neuroprotective compositions and related methods are provided that employ such neuroprotective compounds, and prodrugs of such compounds, to cause dissociation of Nrf2 from a Keap1/Nrf2 complex.

Abstract: The invention provides isolated agents having novel chemical structures and possessing superior activity as derepressors of IAP inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The invention further provides assay methods employing labeled compounds of the invention, especially fluorescent labeled compounds.