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 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 present invention provides for improved therapeutic regimens for treating benign hyperproliferative diseases and cancers. The Egr-1 promoter, long known to be radiation-responsive, has now been shown to be inducible for DNA damaging chemical agents, many of which themselves are used in therapies. Thus, the present invention provides for the advantageous combination of a DNA damaging chemical and an expression vector containing a therapeutic gene driven by the Egr-1 promoter.

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 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: A signaling pathway is identified that involves the activation of phospholipase A2 and protein kinase C in human cells, which in turn confers x-ray induction of the tumor necrosis factor &agr; (TNF) gene. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, as well as the subsequent activation of protein kinase C and TNF gene expression. These phospholipase A2 inhibitors may be used to ameliorate the adverse-effects of radiotherapy associated with TNF production.

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: Chelerythrine is an effective inhibitor of solid tumor growth and is extremely cytotoxic in combination with chemotherapeutic agents that directly damage DNA.

Abstract: The present invention relates generally to the fields of angiogenesis and cancer therapy. More particularly, it concerns the use of anti-angiogenic factors in cancer therapy. The present invention demonstrates that angiostatin or endostatin can sensitize a cell to radiation therapy. Methods and compositions for inhibiting growth, sensitizing a cell to radiotherapy and treating cancer growth by first inhibiting angiogenesis and then employing radiotherapy are described.

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 relates to the interaction of Rad51 and Xrcc3 to form a complex that mediates DNA repair in eukaryotic cells. A functional Rad51/Xrcc3 complex can be introduced into a cell to increase the resistance of the cell to DNA damaging agents. The invention also provides for a clinical application of a regimen combining Rad51 and Xrcc3 to reduce the side effects of radiotherapy and chemotherapy in a patient. In addition, the invention discloses methods for identifying candidate substances that interact with the Rad51/Xrcc3 complex. In another embodiment of the invention, preventing the formation of the Rad51/Xrcc3 complex increases the susceptibility of a cell to DNA damaging agents. This strategy can be used in combination with a DNA damaging agent or factor to kill cancerous cells.

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 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: Disclosed are a variety of compositions and methods for use in specifically targeting the L-selectin or preferably, the E-selectin marker following its cell surface induction, e.g., using ionizing radiation, in tumor vasculature endothelial cells. The compositions and methods described are suitable for use in the delivery of selected agents to tumor vasculature, as may be used in the diagnosis aid therapy of solid tumors.

Abstract: This invention relates to genetic constructs which comprise an enhancer-promoter region which is responsive to radiation, and at least one structural gene whose expression is controlled by the enhancer-promoter. This invention also relates to methods of destroying, altering, or inactivating cells in target tissue by delivering the genetic constructs to the cells of the tissues and inducing expression of the structural gene or genes in the construct by exposing the tissues to ionizing radiation. This invention is useful for treating patients with cancer, clotting disorders, myocardial infarction, and other diseases for which target tissues can be identified and for which gene expression of the construct within the target tissues can alleviate the disease or disorder.

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: Treatment of cells with ionizing radiation is associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, protein kinase C induction and tumor necrosis factor gene expression. The addition of inhibitors of lipoxygenase, such as ketoconazole, prior to irradiation reduces the expression of of tumor necrosis factor while maintaining the expression of other radiation inducible genes, such as Egr-1 and c-jun. In contrast, indomethacin, an inhibitor of cyclooxygenase, enhanced the expression of tumor necrosis factor as well as other radiation inducible genes. The results show that lipoxygenase inhibitors are useful in the treatment of radiation-induced mucositis, dermatitis, pneumonitis, proctitis, and esophagitis. which may be due to the production of cytokines such as TNF.

Abstract: This invention relates to genetic constructs which comprise an enhancer-promoter region which is responsive to radiation, and at least one structural gene whose expression is controlled by the enhancer-promoter. This invention also relates to methods of destroying, altering, or inactivating cells in target tissue by delivering the genetic constructs to the cells of the tissues and inducing expression of the structural gene or genes in the construct by exposing the tissues to ionizing radiation. This invention is useful for treating patients with cancer, clotting disorders, myocardial infarction, and other diseases for which target tissues can be identified and for which gene expression of the construct within the target tissues can alleviate the disease or disorder.

Abstract: The present invention provides a method for delivering ionizing radiation to specific tissues, resulting in the activation of a DNA molecule comprising a radiation responsive enhancer-promoter operatively linked to an encoding region that encodes at least one polypeptide. The radiation source may be will generally be in the form of a radionuclide, capable of gamma or beta emissions. Processes for regulating polypeptide expression and inhibiting tumor growth using such DNA molecules are also provided.