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: 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 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 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 therapeutic combinations and methods of inhibiting the proliferation of cancerous cells, the abnormal growth of cells, and tumor cell growth using the combination of a hedgehog inhibitor with chemotherapy and/or radiation therapy. The present invention also relates to methods of enhancing the antiproliferative effect of chemotherapy and/or radiation therapy in a mammalian cancer patient undergoing either chemotherapy or radiation or a combination of radiation and chemotherapy by co-administering a therapeutically amount of a hedgehog inhibitor, concurrently or sequentially, with the chemotherapy and/or radiation therapy.

Abstract: Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus.

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 present invention concerns methods and compositions involving inhibitors and enhancers of RAD51, a protein involved in homologous recombination. In some embodiments, the present invention concerns methods for stimulating homologous recombination, which has a number of significant research and clinical applications. In certain other embodiments, there are methods for protecting cells using a compound that enhances RAD51 activity. Such enhancers may also be employed to prevent or reduce damage to cells that may be caused by DNA damaging agents. In other embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have particular applications for cancer patients. In some embodiments of the invention, the RAD51 enhancer or inhibitor is a small molecule that directly affects RAD51 activity, such as its ability to promote filament formation.

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 invention relates to treatment of primary and secondary tumors using a therapeutic combination including ionizing radiation and gene therapy comprising mutant-LIGHT. Methods of treating a tumor and inducing an anti-tumor immune response are also provided.

Abstract: In some embodiments, an image-guided radiotherapy apparatus and method is provided in which a radiotherapy radiation source and a gamma ray photon imaging device are positioned with respect to a patient area so that a patient can be treated by a beam emitted from the radiotherapy apparatus and can have images taken by the gamma ray photon imaging device. Radiotherapy treatment and imaging can be performed substantially simultaneously and/or can be performed without moving the patient in some embodiments. The gamma ray photon imaging device can be coupled and movable with respect to any part of a building structure, can be located on a portable frame movable to and from the radiotherapy radiation source and patient, or can take other forms. In some embodiments, the gamma ray photon imaging device can be used for imaging in connection with other types of medical interventions.

Abstract: The present invention provides for improved vectors for use in gene therapy. Utilizing the cancer specific DF3/MUC1 promoter to drive a replication essential gene, vectors are made conditionally replication-competent, permitting wider infection and expression of tumor cells. In addition, therapeutic genes and adjunct therapies further increase anti-tumor efficacy.

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 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 provides a DNA molecule comprising a radiation responsive enhancer-promoter operatively linked to an encoding region that encodes at least one polypeptide. An encoding region can comprise a single encoding sequence for a polypeptide or two or more encoding sequences encoding DNA binding, activation or repression domains of a transcription factor. Processes for regulating polypeptide expression and inhibiting tumor growth using such DNA molecules are also provided.

Abstract: The present invention provides methods of expressing a nucleic acid or producing a proteinaceous composition encoded by a nucleic acid in vascular and cardiovascular cells by administration of a herpesvirus vector. The present invention provides methods of producing a therapeutic benefit in vascular and cardiovascular tissue by administration of a herpesvirus vector. In additional aspects, the invention concerns combination therapies for vascular and cardiovascular diseases comprising administration of a herpesvirus vector and treatment with at least one addition pharmacological agent or surgical procedure.

Abstract: The present invention provides a method of inhibiting a hyperproliferative cell comprising providing to the cell a TNF-&agr; expression construct comprising a chemotherapeutic responsive promoter and a chemotherapeutic selected from doxorubicin, cyclophosphamide, 5-fluorouracil, taxol and gemcitabine.

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: A method for enhancing the efficacy of chemotherapy and/or radiation in the treatment of cancer in animals, particularly humans, is provided wherein certain isocoumarin derivatives which exhibit unique radiosensitization activity and/or chemopotentiation properties are employed in a combination treatment with ionizing radiation and/or chemotherapy.

Abstract: The present invention provides a DNA molecule comprising a radiation responsive enhancer-promoter operatively linked to an encoding region that encodes at least one polypeptide. An encoding region can comprise a single encoding sequence for a polypeptide or two or more encoding sequences encoding DNA binding, activation or repression domains of a transcription factor. Processes for regulating polypeptide expression and inhibiting tumor growth using such DNA molecules are also provided.