Ben notching Since the gegenw Rtige technology is not suitable for the carriage shall foreign genes in most tumor cells, low activity is PCI-24781 CRA-02478 sometimes t of ganciclovir monophosphate is an important limiting factor for the HSV-TK approach to cancer therapy. In addition t Tet TP ganciclovir tumor cells by inhibition of DNA polymerases of DNA replication are involved Similar to how a Herk Mmlicher nucleoside analogues. Consequently, ganciclovir is Haupts Chlich proliferating cells. Since solid tumors often have a low growth fraction, the lack of activity T of this approach to non-proliferating tumor cells is another disadvantage of this approach for the treatment of solid tumors.
5 fluorocytosine has been approved for the treatment of fungal diseases 17-DMAG by selective deamination of fungal cells and fura also investigated in gene therapy strategies, expressed in the E. coli or yeast cytosine deaminase in tumor cells. Human cells do not express cytosine deaminase and Cyt F is well tolerated in humans. Delivery of cytosine deaminase in tumor cells has been shown to sensitize Cyt B, and performed only a few clinical trials to include this gene therapy strategy. E. coli purine nucleoside phosphorylase, PNP takes the difference between human adenosine as substrate and the cutting of the glycosidic bond to an adenine and ribose-phosphate to produce. This difference in substrate specificity T between these two enzymes was used to provide a gene therapy strategy Similar deoxyadenosine to adenine analogues in high-Ma Create e actively enable tumor cells.
Analogues can be prepared from adenine from E. coli PNP to spread easily and to kill, to tumor cells expressing not, E. coli PNP, which is an important feature for gene therapy Ans Approaches to the treatment of cancer due to the difficulty of delivering genes of tumor cells. Because the human cell transport of nucleosides and nucleobases in their membranes that contain purines to facilitate the diffusion of the membranes in both directions, the occasional T ACTION for purine and pyrimidine bases is not dependent on gap junctions Dependent and does not require cell to cell contact, as is the case with ganciclovir nucleotides. Excellent Antitumoraktivit t was with F araAMP against human tumor xenografts in M Mice was observed, even when expressing only 2.5% of tumor cells E.
coli PNP.95 two clinical studies are planned to begin in 2009, the Security and effectiveness of the use of E. coli PNP with araAMP rate F in the treatment of solid tumors. Zus Tzlich to the occasional high activity formed t the approach of E. coli PNP, the adenine analogue toxicity of F and E. coli PNP araAMP has a unique mechanism of action, which the T cells Tion of two non-proliferating and proliferating tumor. 96 two-fluoro-adenine with an analogue of ATP, the RNA and / or inhibits protein synthesis converted. This mechanism to Abt Tion of the cells is different from all currently used cytotoxics and Parker Page 12 manuscripts Chem Rev Author, increases available in PMC 2010 1 July. PA Author Manuscript NIH-PA Author Manuscript NIH Author Manuscript NIH-PA would not be tolerated if the agent is administered systemically. Fluoroadenine was evaluated in mouse models of cancer and is not a selective anti-tumor activity of t are shown. The activity of t this anti-tumor strategy against non-proliferating cells are particularistic