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: The present invention relates to the signalling pathways connecting DNA damage, such as that induced by ionizing radiation or alkylating agents, and phosphorylation by tyrosine kinases.

Abstract: The present invention relates to the signalling pathways connecting DNA damage, such as that induced by ionizing radiation or alkylating agents, and phosphorylation by tyrosine kinases.

Abstract: Methods and compositions for enhancing cancer cell death using therapeutically effective amounts of DNA damaging agent(s) that act in combination to enhance cancer cell death, e.g., nucleic acid precursors, and protein tyrosine kinase inhibitors, e.g., that inhibit EGFR activity. The agents and inhibitors are administered in an amount effective to kill cancer cells, that is, the combined effect is sufficient so that cancer cell death is enhanced. If not administered at the same time, the DNA damaging agent(s) and tyrosine kinase inhibitors are administered close enough in time so they are still able to enhance cancer cell death. The methods and compositions are useful to treat neoplastic disease, e.g., pancreatic cancer.

Abstract: The invention is concerned with fusions of dendritic cells and with tumor or cancer cells. Also provided are methods of making and using these cell fusions, including methods of adoptive immunotherapy as well as methods of stimulating anti-tumor immunity using fused cells and anti-CD3/CD28 antibodies.

Abstract: The invention is concerned with fusions of dendritic cells and antigen presenting cells. Also provided are methods of making and using these cell fusions, including methods of adoptive immunotherapy. The fusions according to the invention can also be used in methods for antigen discovery.

Abstract: The present disclosure demonstrates the successful use of constitutive promoters operatively linked to genes encoding radiosensitizing or radioprotecting factors, administered to cells, tissues, or patients in conjunction with radiation exposure. Also disclosed are pharmacological preparations to be used to increase the levels of radiosensitizing compounds such as TNF-?, or radioprotective compounds such as MnSOD, in specified tissues or tumors of a subject.

Abstract: The present disclosure provides methods of identifying and making compounds and pharmaceutical compositions thereof that inhibit the interaction between MUC1 and Abl. The invention also provides in vivo, in vitro, and ex vivo methods of inhibiting such an interaction. Also featured are in vitro and in vivo methods of stimulating the Abl-dependent apoptotic pathway in cells expressing MUC1. In such methods, the compounds, compositions, and methods described herein are generally useful in the treatment of various cancers. The disclosure also provides methods for inhibiting Abl, and such methods, and compounds and compositions for use in the methods are generally useful for the treatment of cancers, inflammatory conditions, atherosclerotic lesions, and neurologic disorders.

Abstract: The present invention is directed to novel methods of enhancing the effectiveness of DNA damaging agents by exposing cells to viruses prior to or during exposure to the damaging agent. In certain embodiments of the invention, the DNA damaging agent is ionizing radiation, the virus is an adenovirus, and the increase in cell killing is synergistic when compared to radiation alone.

Abstract: Disclosed are methods of synergistically inhibiting growth of a glioma cell comprising contacting the cell with temozolomide and TNF?, or with temozolomide, TNF?, and radiation. Also disclosed are methods of synergistically inhibiting growth of a glioma in a human cancer patient comprising administering temozolomide and TNF?, or with temozolomide, TNF?, and radiation. Pharmaceutical combinations and therapeutic combinations suitable for use in the methods of the invention are also disclosed.

Abstract: The present invention relates to methods of enhancing death receptor-induced apoptosis in MUC1 expressing cells comprising contacting the MUC1 expressing cells with an effective amount of a MUC1 antagonist.

Abstract: The invention is concerned with fusions of dendritic cells and antigen presenting cells. Also provided are methods of making and using these cell fusions, including methods of adoptive immunotherapy. The fusions according to the invention can also be used in methods for antigen discovery.

Abstract: The present invention provides for chimeric proteins comprising a MUC1 extracellular (MUC1-EC) polypeptide and a carrier polypeptide that function as traps for MUC1 ligands.

Abstract: The invention provides methods of screening to identify compounds that modulate the ability of a protein to translocate to the mitochondria when a cell is subjected to cellular stress. Such compounds can be useful to modulate the level of apoptosis in a cell. For example, compounds identified according to the methods described herein can be used to treat disorders characterized by excessive apoptosis, e.g., a neurological disorder, or insufficient apoptosis, e.g., cancer.

Abstract: The present invention relates to methods of inducing expression of a polynucleotide encoding a therapeutic polypeptide, e.g., TNF-?, in a cell comprising contacting the cell with a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding the polypeptide, and at least one chemotherapeutic agent, wherein the chemotherapeutic agent induces expression of the polypeptide. The invention also relates to methods of inhibiting a neoplastic cell, comprising contacting the cell with a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-? and a chemotherapeutic agent. The present invention further relates to methods of inhibiting or reducing the growth of a tumor in a subject, comprising co-administering to the subject a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-? and a chemotherapeutic agent, wherein the co-administration inhibits or reduces the ability of the tumor to grow.

Abstract: The present invention relates to the signalling pathways connecting DNA damage, such as that induced by ionizing radiation or alkylating agents, and phosphorylation by tyrosine kinases.

Abstract: Recombinant pox viruses capable of expressing an immunogenic fragment of the MUC1 tumor-associated antigen are disclosed. The recombinant viruses can be used as vaccines to prevent the establishment of or treat tumors or pre-tumorous cells expressing the MUC1 tumor-associated antigen. The vaccines can be provided as an admixture comprising: (1) a recombinant pox virus encoding the immunogenic fragment of the MUC1 tumor-associated antigen, and (2) a recombinant pox virus encoding a T-cell co-stimulatory factor. The vaccine admixture can be used, e.g., to prevent establishment of tumors or pre-tumorous cells expressing the MUC1 tumor-associated antigen. The MUC1 specific cytotoxic T-cells can be isolated and expanded and used in a method for treating a host having a tumor expressing MCU1 positive tumor cells.

Abstract: Methods for improved administration and dosing of DPD inhibitors in combination with 5-FU and/or 5-FU prodrugs are provided, comprising first administering to a patient in need thereof a DPD inhibitor that substantially eliminates activity of the enzyme and thereafter administering 5-FU or a 5-FU prodrug, wherein the level of 5-FU or 5-FU prodrug is in substantial excess of DPD inhibitor in the patient.

Abstract: The present invention relates to the signalling pathways connecting DNA damage, such as that induced by ionizing radiation or alkylating agents, and phosphorylation by tyrosine kinases.

Abstract: The invention provides methods of reducing or preventing oxidative stress-induced cell death by contacting a cell with a compound that inhibits the kinase activity and/or the mitochondrial translocation of c-Abl. The methods of the invention can be used to treat individuals individual diagnosed as having or being at risk of contracting a disorder characterized by excessive oxidative stress-induced cell death.