[Influence of the thymidine phosphorylase (platelet-derived endothelial cell growth factor) on tumor angiogenesis. Catalytic activity of enzyme inhibitors]. / Wplyw fosforylazy tymidynowej (plytkopochodnego czynnika wzrostu komórek sródblonka) na angiogeneze guzów. Inhibitory aktywnosci katalitycznej enzymu.

Thymidine phosphorylase, also known as platelet-derived endothelial cell growth factor, is a potent angiogenic factor. Thymidine phosphorylase is overexpressed in various human tumors and plays an important role in angiogenesis. A novel inhibitor of thymidine phosphorylase (TP), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI) is about 1000-fold more active than 6-amino-5-chlorouracil, one of the most potent TP inhibitors to 1999 year. Thymidine phosphorylase is also inhibited by 5'-O-trityl-inosine (KIN59) and related compounds, 2-deoxy-L-ribose and glycosides isolated from the bark of Symplocos racemosa.

[Influence of the selected pyrimidine compounds on the activity of thymidine phosphorylase from normal and tumor endometrial cells]. / Wplyw wybranych zwiazków pirymidynowych na aktywnosc fosforylazy tymidynowej komórek endometrialnych prawidlowych i nowotworowych.

OBJECTIVES: The aim of this study was to evaluate the influence of the selected pyrimidine compounds on the activity of thymidine phosphorylase (TP) of normal and tumor endometrial cells. MATERIALS AND METHODS: Influence of 28 chemical compounds on the TP activity in the cytosol of the endometrial cells was studied by the spectrophotometric method. The studied group comprised postmenopausal women with endometrial cancer: adenocarcinoma endometrialis (Adeno Ca E). The second group included women with normal endometrium after surgery due to non-oncologic reasons. RESULTS: The most potent inhibitor of TP activity from cancer and endometrium was synthesized 5-bromo-6-acetyloaminouracil, which at the 0.2 mM concentration, by 0.2 mM concentration thymidine reduced the cytosol TP activity by about 80%. 5-bromo-6-aminouracil, 5-nitrouracil and 5-bromouracil reduced this TP activity in statistically significant manner. From among synthesized 1-N-allyloxymethylpyrimidine derivatives 1-N-allyloxymethylthymine was the strongest inhibitor of the TP activity in endometrium, and 1-N-allyloxymethyl-4-hydrokxy-5-nitro-6-oxopyrimidine in endometrial cancer respectively. The most potent activators of TP in endometrial cancer was 5-bromodeoxyuridine and 1-N-allyloxymethyl-5-nitrouracil, which increased the TP activity about 100%. 5-fluorodeoxyuridine, 5-jododeoxyuridine and 2'-deoxyuridine activated the TP in statistically significant manner too, but stronger in case of endometrial cancer than in normal endometrium. The synthesized 5-bromo-6-acetyloaminouracil strongly inhibited the TP activity of endometrial cells and might be useful in reducing endometrial cancer angiogenesis. On the other hand 5-bromodeoxyuridine and the synthesized 1-N-allyloxymethyl-5-nitrouracil might increase the effect of antitumor therapy with the cytostatics. These conclusions ought to be confirmed by analyzing more tumor cases.

[The thymidine phosphorylase as the platelet-derived endothelial cell growth factor of endometrial cancer]. / Fosforylaza tymidynowa jako plytkopochodny czynnik wzrostowy komórek sródblonka raka endometrium.

OBJECTIVES: The aim of the study was to assess the correlation between the activity of thymidine phosphorylase (TP) and the platelet derived-endothelial cell growth factor (PD-ECGF) expression in endometrial carcinoma. METHODS: The study group consisted of 40 tissue samples taken from patients with endometrial carcinoma, who underwent surgery in First Clinic of Gynecology and Oncologic Gynecology of Medical University in Lodz. The control tissue samples were taken from patients who were operated on for non-oncologic reason. The activity of TP was measured by the spectrophotometric method in the cytosol of tumor cells, and the immunohistochemical staining of PD-ECGF was performed in the same tumors. The results of TP activity were compared with the microvessel density (MD) assessed by immunohistochemical analysis and with clinico-pathological features like tumor grade and FIGO stage. RESULT: A positive correlation between the enzyme activity and expression of TP/PD-ECGF protein was found. Moreover a significantly higher TP activity was confirmed in malignant tumors from endometrial cancer patients when compared to the controls. A positive correlation between the enzyme activity and MD was also stated, but there was no connection to the grade of tumors and FIGO stage. Since the TP activity proved to be related to PD-ECGF expression and angiogenesis, we can state that TP seems to be an active form of PD-ECGF growth factor in endometrial carcinoma. This is in agreement with the results of many publications on other malignancies. The proper modulation of this activity may be useful in adjuvant therapies.

[Immunological aspects of corneal graft rejection and own experience in immunosuppressive therapy in high risk patients]. / Immunologiczne aspekty choroby przeszczepu oraz doswiadczenia wlasne ze stosowania terapii immunosupresyjnej u pacjentów wysokiego ryzyka.

The aim of the study was to present factors responsible for immune privilege of corneal graft, pathogenesis of immunological corneal graft rejection, and the influence of immunosuppressive therapy on keeping clarity of corneal graft. We also present retrospective evaluation of prophylactic immunosuppressive therapy in high-risk patients and in cases of graft rejection, in group of patients after corneal transplantation performed in Department of Ophthalmology in years 2001-2003. 349 cases of penetrating keratoplasty, lamellar or penetrating with limbal transplantation were analyzed. Condition requiring keratoplasty, surgical procedures, profile of immunosuppressive therapy, number of recurrences of corneal graft rejection and changes of visual acuity were evaluated. Immunosuppressive therapy with oral corticosteroids and systemic Cyclosporine allow to keep clarity of corneal graft and useful visual acuity in 60% cases of high-risk patients.