Abstract: Chemotherapeutic and Radiation sensitizing agents which target tumor cells, specifically, based on the elevation of enzyme pathways, provide highly selective drug therapy. These agents are combined with modulating doses of cytidine deaminase inhibitors to increase selectivity. Furthermore, high doses of these cytidine deaminase inhibitors have the potential of counteracting the aggressive and metastatic characteristics of pancreatic tumors. For tumors with high levels of cytidine deaminase, such as pancreatic tumors, this elevation provides a therapeutic approach with prodrugs that require deamination for their activation. For tumors with high levels of uridine/cytidine kinase, a different class of pyrimidine analogs can be activated selectively in tumors for a therapeutic advantage.

Abstract: Zebularine has hypomethylating activity, and can be used to inhibit, reverse, and/or reduce DNA methylation in vivo and in vitro. Methods are provided for treating methylation-linked conditions through the application of 2-pyrimidinone derivatives, such as Zebularine. Compositions, including pharmaceutical compositions, comprising such derivatives are also provided. Also provided are kits for use in inhibiting DNA methylation, which kits include an amount of a 2-pyrimidinone derivative.

Abstract: Chemotherapeutic and Radiation sensitizing agents which target tumor cells, specifically, based on the elevation of enzyme pathways, provide highly selective drug therapy. These agents are combined with modulating doses of cytidine deaminase inhibitors to increase selectivity. Furthermore, high doses of these cytidine deaminase inhibitors have the potential of counteracting the aggressive and metastatic characteristics of pancreatic tumors. For tumors with high levels of cytidine deaminase, such as pancreatic tumors, this elevation provides a therapeutic approach with prodrugs that require deamination for their activation. For tumors with high levels of uridine/cytidine kinase, a different class of pyrimidine analogs can be activated selectively in tumors for a therapeutic advantage.

Abstract: A method of treating tumors with radiation is disclosed, wherein the tumor is sensitized by administering a tumor sensitizing agent comprising 5-chloro-2?-deoxycytidine, 4-N-methyl FdC and a cytidine deaminase inhibitor to a patient having the tumor. The tumor is then subjected to radiation.

Abstract: A method of treating tumors with radiation is disclosed, wherein the tumor is sensitized by administering a tumor sensitizing agent comprising 5-chloro-2′-deoxycytidine, 4-N-methyl FdC and a cytidine deaminase inhibitor to a patient having the tumor. The tumor is then subjected to radiation.

Abstract: The present invention pertains to combination radio therapy of tumors and more specifically to pharmaceutical compositions, and methods of treatment by gene therapy designed to sensitize tumors in animals, notably humans, and render them more susceptible to radiation, thus significantly reducing the amount of radiation required to kill neoplastic cells while at the same time making the radiation far more tissue specific to the tumor site.

Abstract: The present invention pertains to combination radio therapy of tumors and more specifically to pharmaceutical compositions, and methods of treatment by gene therapy designed to sensitize tumors in animals, notably humans, and render them more susceptible to radiation, thus significantly reducing the amount of radiation required to kill neoplastic cells while at the same time making the radiation far more tissue specific to the tumor site.

Abstract: Tumors are sensitized to radiation by administration of 5-chlorodeoxycytidine (5-CldC) or 5-halo-2'-halo-2'-deoxy-cytidine or -uridine derivatives. Tetrahydrouridane (H.sub.4 U) and/or 2'-deoxytetrahydrouridine (dH.sub.4 U) is preferably coadministered with the deoxycytidine derivative to inhibit deamination of the deoxycytidine derivatives. Optional pre- or concurrent treatment with agents to reduce the amount of competing metabolites to favor CldC, such as 5-fluorodeoxyuridine, results in a procedure that significantly increases the dose effects of X-radiation. Pharmaceutical compositions suitable for the sensitization of tumors to radiation are also disclosed.