Franco Milano

Effects of gemcitabine in normal and transformed human lung cell cultures: cytotoxicity and increase in radiation sensitivity.

Aims and Background Several anticancer drugs increase cell sensitivity to irradiation. Gemcitabine (2′, 2′ difluorodeoxycytidine) decreases the cellular dNTP pools and thus significantly increases the sensitivity to the DNA damaging effects of low-dose radiation. In this study we have investigated whether gemcitabine may play a role as radiosensitizer also in lung adenocarcinoma treatment. Methods & Study Design We studied this nucleoside analogue in normal and transformed human cell lines (fetal lung and lung adenocarcinoma). After drug treatment, cell lines were irradiated with different doses. Cell damage following drug treatment and/or irradiation was assessed by measuring intracellular ATP level and by the colony forming assay. Results The two cell lines significantly differed in their sensitivity to the toxic effects of the drug; the normal cell line was much more resistant than its transformed counterpart. This difference was observed in both assays, although it was more evident in the colony forming assay. A low radiation dose (50-100 cGy) did not cause any significant damage to transformed cells; normal cells were more resistant and doses up to 500 cGy caused little damage. However, when transformed cells were pretreated for three hours with gemcitabine, even a nontoxic concentration of the drug (1-10 nM) caused a marked sensitization of the cells to irradiation (50-100 cGy). The radiosensitizing effect of gemcitabine could be observed also in normal cells, although these cells were more resistant to the damaging effects of both anticancer treatments. Conclusions This study demonstrates that gemcitabine, a chemotherapeutic agent already used in the clinic, could be proposed as a radiosensitizer for radiation therapy of lung adenocarcinoma, having a clearly potentiating effect on low-dose radiation.

Conferring drug resistance by MDR1 gene transfection increases susceptibility to irradiation and lipid peroxidation in 3T3 cell line

This study was performed to test the hypothesis that conferring multiple drug resistance reduces cell susceptibility to irradiation and iron-stimulated lipid peroxidation. Multidrug resistant (PN1A) and parental drug sensitive (PSI-2) cell lines were exposed to ADP-Fe or Ascorbate-Fe complexes at 37 degrees C and to irradiation. Lipid peroxidation was estimated by the TBA test, whereas x-ray effect was estimated by clonogenic assay. Cell glutathione-S-transferase (GST), total and Se-dependent glutathione peroxidase (GSH-Px) activities, and glutathione and vitamin E were measured. PN1A produced more peroxides than PSI-2 after exposure to iron complexes and formed fewer colonies after irradiation. Higher activities of GST and total and Se-GSH-Px were observed in PN1A. Vitamin E and total glutathione did not differ in the two cell subclones. These data show that the induction of the mdr1 phenotype by transfection of mdr1 gene in 3T3 cells increases susceptibility to irradiation and iron stimulated lipid peroxidation.

EMITEL e-Encyclopaedia of Medical Physics - Project Development and Future

The e-Encyclopaedia for Medical Physics with Multilingual Dictionary EMITEL has been launched 6 months ago (www.emitel2.eu). This international project attracted more than 250 specialists from 35 countries and established itself as the largest international project in the profession. The paper describes the main phases of EMITEL, its current use and the planned future development.

Magnetic Resonance Imaging and Ultrasound Experience from the EMIT and EMITEL e-Learning and e-Encyclopedia Projects

As part of two European Union funded projects we have developed Magnetic Resonance Imaging and Ultrasound materials for e-learning and an e-encyclopedia. The e-learning modules were developed for the EMIT project which aimed to produce training and e-learning materials to facilitate core training for medical physics in the fields of Magnetic Resonance Imaging and Ultrasound. The training modules were based on development of skills and competencies through practical performance of key tasks. Each module included a list of competencies, structured timetable, student workbook and an image database. The e-encyclopedia was developed for the EMITEL project. The encyclopedia is aimed at MSc level or above and aims to provide extensive coverage of Magnetic Resonance Imaging, Ultrasound and other areas of medical physics. Each e-Encyclopedia entry includes key text, figures (images or diagrams), links to other related entries and key references or external web links.