Abstract: We have discovered that administering anti-ceramide antibody treats and prevents an array of diseases mediated by cytolytic T lymphocyte (CTLs)-induced killing and by damage to endothelial microvasculture, including radiation-induced GI syndrome, Graft vs. Host diseases, inflammatory diseases and autoimmune diseases. We have also discovered new anti-ceramide monoclonal antibodies, that have therapeutic use preferably in humanized form to treat or prevent these diseases.

Abstract: The present application provides substituted purine derivatives and related compounds of the formulas shown. These compounds are useful as inhibitors of HSP90, and hence in the treatment of related diseases. (Formulae) Z1-Z3, Xa-Xc, X2, X4, Y and R are as defined in the specification.

Abstract: Disclosed is a method for searching, identifying, or validating a marker CACNA2D1 of tumor-initiating cells. The method comprises a step of immunizing an animal using HEP-12 cells originating from a recurrent tumor and rich in originating cells. Also disclosed is a monoclonal antibody specially recognizing CACNA2D1 or antigen-binding fragments thereof, and the use thereof for treating or preventing tumors or diseases or conditions related to CACNA2D1.

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea compounds (referred herein as “TBAP compounds”) that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.); and to treat disorders including: proliferative disorders; cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma); inflammation; immunological disorders; viral infections; fibrotic disorders; disorders associated with a mutated form of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of RAF (e.g., BRAF, CRAF, etc.

Abstract: The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Abstract: Compounds of formula: in which R4 is chosen from substituted phenyl, optionally substituted naphthylene, optionally substituted anthracene and optionally substituted aromatic heterocycle, are useful as analgesics.

Abstract: Some aspects of this invention are based on the recognition that reversible protein multimers in which monomeric proteins are conjugated to a carrier molecule via chelation complex bonds are stable under physiological conditions and can be dissociated in a controlled manner under physiological, nontoxic conditions. Accordingly, such protein multimers are useful for a variety of in vitro, ex vivo, and in vivo application for research, diagnostics, and therapy. Some aspect of this invention provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized.

Abstract: The instant disclosure provides antibodies that specifically bind to human CTLA-4 and antagonize CTLA-4 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Abstract: The invention provides compounds, methods, pharmaceutical compositions, and kits for the treatment of proliferative disorders such as cancer. In one aspect, the methods comprise compounds that inhibit the activity of protein kinases, such as cell division cycle (Cdc) kinase. In another aspect, the methods comprise compounds that inhibit Cdc7 and/or Dbf4 activity. In another aspect, the methods comprise compounds that exhibit anti-proliferative properties useful in treating diseases such as cancer. Compounds useful for any of the methods include compounds of the Formula (A) or (B): or pharmaceutically acceptable salts thereof. Exemplary compounds of Formula (A) or (B) include granaticin A, granaticin B, dihydrogranaticin A, dihydrogranaticin B, medermycin, and actinorhodin.

Abstract: The present invention provides pluripotent and multipotent stem cells, including embryonic stem cells, induced pluripotent stem cells, adult stem cells and other progenitor cells, that have been modified to contain an inducible cancer-specific suicide gene construct that, upon induction, selectively kills stem- or progenitor-cell-derived cancerous cells without significant effect on healthy tissues or other (noncancerous) cells derived from such cells. This suicide gene construct expresses a dominant negative MYC-interfering protein (D-MIP) that acts as a tumor suppressor in cancer cells without significant deleterious effects on healthy cells and tissues. The suicide gene construct can also be used in gene therapies that produce cancers arising in association with the presence of the gene therapy vector and likewise discriminates between killing of cancerous cells and non-cancerous cells modified with a gene therapy vector.

Abstract: The present disclosure, among other things, provides a composition of a particle including a substrate; at least a first condensation layer comprising at least a first dopant entity; and at least a second layer comprising a second dopant entity. In some embodiments, different dopant entities are included in different layers. In some embodiments, such dopant entities are or comprise detectable entities. This, in some embodiments, provided technologies achieve multi-modality particles. Among the many advantages of provided technologies include the ability to image particles by a plurality of distinct imaging modalities and/or in a plurality of contexts (e.g., pre-surgical, intraoperative and/or post-surgical environments).

Abstract: The present invention pertains generally to the field of organic chemical synthesis, and in particular to certain methods for the synthesis of 8-(4-aminophenyoxy)-4H-pyrido[2,3-b]pyrazin-3-one and related compounds (denoted herein as (3)) from 4-(4-aminophenyoxy)pyridine-2,3-diamine and related compounds (denoted herein as (1)), by reaction with glyoxylic acid (denoted herein as (2)). The compounds (3) are useful in the synthesis of known anti-cancer agents, such as 1-(5-tert-butyl-2-(4-methyl-phenyl)-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea.

Abstract: The present invention relates to adenovirus E4ORF1 gene and to endothelial cells engineered to express the E4ORF1 gene. The present invention also relates to uses of the E4ORF1 gene, and cells expressing the E4ORF1 gene, and to compositions comprising the E4ORF1 gene, or comprising cells expressing the E4ORF1 gene.

Abstract: The present invention relates to methods, kits, and compositions for detecting and/or diagnosing metastatic potential of cancer cells or for evaluating prognosis in a patient with cancer by detection of the protein expression level of an HLA class I molecule and/or the copy number variation of a polynucleotide encoding the HLA class I molecule. The present invention also relates to the use of the protein expression level of an HLA class I molecule and/or the copy number variation of a polynucleotide encoding the HLA class I molecule as a prognosis biomarker and metastasis predictive biomarker of cancer.

Abstract: The disclosure relates to Compounds of Formula (1): and pharmaceutically acceptable salts thereof wherein Z1, Z2, Z3, Xa, Xb, Xc, Y, X2, and X4 are as defined herein, compositions comprising an effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof, and methods to treat or prevent a condition, such as cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof.

Abstract: Methods and compositions for modulating blood-neural barrier (BNB) for the treatment of CNS conditions such as edema, and for increased drug delivery efficacy across the BNB. The present invention further relates to improved tPA treatment of ischemic cerebrovascular and related diseases in combination with antagonism of the PDGF signaling pathway. The inventive method and composition is particularly suitable for conjunctive therapy of ischemic stroke using tPA and an anti-PDGF-C antagonist or an anti-PDGFR-? antagonist.

Abstract: The invention provides liposomes containing nonglycosidic ceramides within their bilayers, and compositions thereof. These liposomes activate murine iNKT cells and induce dendritic cell (DC) maturation, both in vitro and in vivo at an efficacy that is comparable to their corresponding soluble nonglycosidic ceramides. Also provided are methods for treating diseases using the liposomes and compositions of the invention.

Abstract: Specific binding members, particularly antibodies and fragments thereof, which bind to transforming growth factor beta 1 (TGF-?1) are provided, particularly recognizing human and mouse TGF-?1 and not recognizing or binding TGF-?2 or TGF-?3. Particular antibodies are provided which specifically recognize and neutralize TGF-?1. These antibodies are useful in the diagnosis and treatment of conditions associated with activated or elevated TGF-?1, including cancer, and for modulating immune cells and immune response, including immune response to cancer or cancer antigens. The anti-TGF-?1 antibodies, variable regions or CDR domain sequences thereof, and fragments thereof may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof. Antibodies of this type are exemplified by the novel antibodies hereof, including antibody 13A1, whose sequences are provided herein.

Abstract: Some aspects of this invention are based on the recognition that reversible protein multimers in which monomeric proteins are conjugated to a carrier molecule via chelation complex bonds are stable under physiological conditions and can be dissociated in a controlled manner under physiological, nontoxic conditions. Accordingly, such protein multimers are useful for a variety of in vitro, ex vivo, and in vivo application for research, diagnostics, and therapy. Some aspect of this invention provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized.

Abstract: Expression of proteolytically active, high molecular weight ADAM protease is relatively increased in tumor cells that also express the putative tumor stem cell marker CD133. An antibody or antibody fragment such as 8C7 monoclonal antibody may be used to selectively bind to proteolytically active, high molecular weight ADAM10 protease to thereby detect tumor cells and also as a therapeutic agent for treating cancers, tumors and other malignancies inclusive of leukemia, lymphoma, lung cancer, colon cancer, adenoma, neuroblastoma, brain tumor, renal tumor, prostate cancer, sarcoma and/or melanoma.