The influence of pH and temperature on the stability of N-[(piperidine)methylene]daunorubicin Hydrochloride and a comparison of the stability of daunorubicin and its four new amidine derivatives in aqueous solutions.

The influence of pH and temperature on the stability of N-[(piperidine)methylene]daunorubicin hydrochloride (PPD) was investigated. Degradation was studied using an HPLC method. Specific acid-base catalysis of PPD involves hydrolysis of protonated molecules of PPD catalyzed by hydrogen ions and spontaneous hydrolysis under the influence of water zwitterions, unprotonated molecules, and monoanions of PPD. The thermodynamic parameters of these reactions, energy, enthalpy, and entropy, were calculated. Also, the stability of daunorubicin and its new amidine derivatives (piperidine, morpholine, pyrrolidine, and hexahydroazepin-1-yl) in aqueous solutions was compared and discussed.

Comparison of semiquantitative metabolic parameters of the primary tumor obtained in PET/CT with 18F-FDG and 18F-FLT in patients with cervical cancer.

AIM: The aim of the study was to compare semiquantitative metabolic parameters of primary tumor assessed in vivo in 18F-FDG- and 18F-FLT in cervical cancer patients. MATERIAL & METHODS: 39 patients with histologically confirmed cervical cancer underwent PET/CT scans acquired on separate days 60 min after i. v. injection of 364 ±â€Š75 MBq of 18F-FDG and 259 ±â€Š40 MBq of 18F-FLT. The reconstructed PET images were evaluated using a dedicated workstation for primary tumor semiquantitative parameters: SUVmax, MTV, TLG (for 18F-FLT-TLP) and heterogeneity (AUC-CSH). Wilcoxon-Mann-Whitney test and ROC curves were used for statistical analysis. Based on data from the local cancer registry and 3y- to -5y follow up patients were divided into 2 groups with regard to prognosis. Also differences between histopathological type and FIGO classification in two tracers were assessed. RESULTS: Depending on PET/CT results, patients were divided into 3 groups: group 1 with disease limited only to the cervix, group 2 with disease limited to the cervix and iliac lymph nodes, and group 3 with disseminated disease. Statistically significant differences were found between keratinizing and non-keratinizing SCC in SUVmax (p = 0.03) and AUC-CSH (p = 0.04) only in 18F-FLT-PET/CT. Following cut-off values for nodal involvement in SUVmax, MTV, TLG/TLP and AUC-CSH were calculated using ROC curves: 13.5, 39.22, 255.94, 0.59 respectively for 18F-FDG and 12.1, 37.59, 140.01, 0.46 respectively for 18F-FLT. Higher values in both tracers in MTV and TLG/TLP were found in a group with worse prognosis. CONCLUSION: This preliminary study suggests that higher values in MTV and TLG/TLP in both tracers might be associated with worse outcome in cervical cancer patients.

Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) cells are characterized by failures in the apoptosis pathway and increased proliferation, resulting in the progressive accumulation of B-lymphocytes in blood. Despite the wide range of antileukaemic drugs, CLL remains an incurable disease. However, a breakthrough is expected which will allow more effective treatment. OBJECTIVE: The study investigates the influence of poly(propyleneimine) (PPI) dendrimer with peripheral amino groups, 30% of which were coated with maltotriose (PPI-G4-OS-Mal-III), on CLL cells, and demonstrates that it acts through the induction of the apoptotic mechanism. It is important to note that the dendrimer was used as a drug itself and not as a drug carrier. METHOD: CLL and normal lymphocytes were treated in vitro with the dendrimer, either alone or in combination with fludarabine (FA). The percentages of apoptotic and necrotic cells, and the protein expression, were checked using a flow cytometer. Gene expression was screened using a two-colour microarray with 60-mer probes. RESULTS: The results confirm that PPI-G4-OS-Mal-III influences the viability of CLL cells in vitro and does not exert any significant harmful effect on normal lymphocytes. The dendrimer appears to significantly influence gene and protein expression in CLL cells. CONCLUSION: Since dendrimers can be specifically targeted, they may be very effective in CLL therapy, especially since in vitro PPI-G4-OS-Mal-III has been found to have stronger effect than fludarabine.