Abstract. Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether CPEC enhances the therapeutic ratio of gemcitabine and irradiation in human pancreatic BxPC-3 xenografts and in rat syngeneic L44 lung tumours. These models were selected because gemcitabine and radiation are used to treat both pancreatic and lung cancer patients and both models differ in growth capacity and in gemcitabine-induced radiosensitisation. A profound dose-dependent CTP-depletion was observed after a single injection of CPEC in both tumour tissue and in normal jejunum. In both models, CPEC alone induced a slight but significant tumour growth delay. The combination of CPEC with gemcitabine, at time intervals that showed CTP-depletion after CPEC, enhanced neither tumour growth delay nor toxicity as compared to gemcitabine alone. In addition, no beneficial effect of CPEC was observed in combination with gemcitabine and radiation. These results suggest that CPEC and gemcitabine alone as well as in combination with radiation target a similar cell population in both tumour models. In conclusion, future clinical development of CPEC as a modulator of gemcitabine combined with radiation is unlikely.

The problem of prevention and treatment of infectious diseases in infectious and non-infectious clinics is one of the priorities in practical public health. The application of phage preparations, as antimicrobial medioprophylactic remedies against staphylo-and streptococcal infections seems to be an alternative to antibiotics and sulfonamide preparations. Pronounced tendency of circulating pathogenic bacterial strains towards reducing sensitivity to antibiotics, also caused by irrational use of the latter, further confirmed our decision to create a new phage preparation. Based on the conducted studies the new variant of Fersis, an active, multivalent phage preparation, consisting phages against staphylococci (S. aureus, S. epidermidis) and streptococci (S. pyogenes, S. viridians, S. sanguis, S. salivarius, S. agalacticae) causing oral cavity infectious diseases, has been prepared.