Activity of tyrosine kinase inhibitor Dasatinib in neuroblastoma cells in vitro and in orthotopic mouse model.

Stage 4 neuroblastoma (NB) is a devastating childhood cancer whose poor outcome has remained essentially unchanged in the last 20 years. Receptor tyrosine kinases have important roles in the control of proliferation, differentiation and apoptosis of NB cells. Thus, we tested the activity of second-generation tyrosine kinase inhibitor Dasatinib in human NB cell lines in vitro and in an orthotopic mouse model. Dasatinib inhibited cell viability with an IC(50) in the submicromolar range in 7 of 10 tested cell lines. In sensitive cells, Dasatinib reduced anchorage-independent growth and, in some instances, induced senescence and apoptosis. In HTLA-230 cells, Dasatinib treatment caused down-regulation of c-Kit and c-Src phosphorylation in conjunction with strong inhibition of Erk1/2 and Akt activity. To test the efficacy of Dasatinib in vivo, HTLA-230 and SY5Y cells were orthotopically injected in the adrenal gland of nude mice and drug treatments carried out until day 40. In mice injected with HTLA-230 cells, tumour growth was significantly inhibited at the dose of 30 mg/(kg day) when treatment was started 7 days after injection. In animals injected with SY5Y cells that were exquisitely sensitive in vitro (IC(50)= 92 nM), the antitumour effect of Dasatinib was observed at the dose of 60 mg/(kg day) but only when treatment was started 1 day after injection. However, the anti-tumour effect of Dasatinib in vivo was partial in both orthotopic models, emphasizing the importance of testing candidate new drugs in animal environments closely mimicking the human tumour.

No effects of UMTS exposure on the function of rat outer hair cells.

UMTS communication devices are becoming common in everyday use. This could raise public concern about their possible detrimental effects on human health. The aim of this study, in the framework of the EMF nEAR Project, was to evaluate possible influence of UMTS electromagnetic fields (EMF) exposure on cochlear outer hair cells' (OHCs) functionality in laboratory animals. Forty-eight male Sprague-Dawley rats were locally exposed (right ear) or sham-exposed to a controlled UMTS EMF, frequency of 1946 MHz, at SAR level of 10 W/kg, 2 h a day, 5 days a week, for 4 weeks. A group of 12 rats treated with kanamycin (KM) was also included as positive control. Rats were tested by recording Distortion Product Otaoacoustic Emissions (DPOAEs), a non-invasive test capable of assessing the status of the OHCs in the inner ear. DPOAEs were performed before, during (one or three times a week) and after (1-week) exposure to the EMF. The analysis of the data shows that no statistically significant differences were found between the audiological signals recorded from the different experimental groups. The ototoxic effect of KM has been confirmed.

Possible combined effects of 900 MHZ continuous-wave electromagnetic fields and gentamicin on the auditory system of rats.

The aim of this study was to evaluate the cochlear functionality of Sprague-Dawley rats exposed to electromagnetic fields at 900 MHz and to gentamicin by distortion product otoacoustic emissions, which are a well-known indicator of the status of the cochlea's outer hair cells. A population of 32 rats was divided into four groups: group 1 was treated with daily intramuscular injections of 150 mg/kg body weight gentamicin for 15 days; group 2 was treated with daily intramuscular injections of 150 mg/kg body weight gentamicin for 15 days and exposed to electromagnetic fields; group 3 was exposed to electromagnetic fields; group 4 was sham-exposed. Rats were exposed 2 h/day, 5 days/week for 4 weeks at a local SAR of 4 W/kg in the ear (continuous wave at 900 MHz). Distortion product otoacoustic emissions tests were carried out before, during and after the combined exposure. The analysis of the data showed no subchronic exposure to electromagnetic fields on the inner auditory system of rats in either normal ears or ears exposed to a well-recognized pathological agent.

Electromagnetic fields from mobile phones do not affect the inner auditory system of Sprague-Dawley rats.

The auditory system is the first biological structure facing the electromagnetic fields emitted by mobile phones. The aim of this study was to evaluate the cochlear functionality of Sprague-Dawley rats exposed to electromagnetic fields at the typical frequencies of GSM mobile phones (900 and 1800 MHz) by distortion product otoacoustic emissions, which are a well-known indicator of the status of the cochlea's outer hair cells. A population of 48 rats was divided into exposed and sham-exposed groups. Three sets of four loop antennas, one for sham-exposed animals and two for exposed animals, were used for the local exposures. Rats were exposed 2 h/day, 5 days/week for 4 weeks at a local SAR of 2 W/kg in the ear. Distortion product otoacoustic emissions tests were carried out before, during and after the exposure. The analysis of the data shows no statistically significant differences between the audiological signals recorded for the different groups.

Effects of 900 MHz electromagnetic fields exposure on cochlear cells' functionality in rats: evaluation of distortion product otoacoustic emissions.

In recent years, the widespread use of mobile phones has been accompanied by public debate about possible adverse consequences on human health. The auditory system is a major target of exposure to electromagnetic fields (EMF) emitted by cellular telephones; the aim of this study was the evaluation of possible effects of cellular phone-like emissions on the functionality of rat's cochlea. Distortion Products OtoAcoustic Emission (DPOAE) amplitude was selected as cochlea's outer hair cells (OHC) status indicator. A number of protocols, including different frequencies (the lower ones in rat's cochlea sensitivity spectrum), intensities and periods of exposure, were used; tests were carried out before, during and after the period of treatment. No significant variation due to exposure to microwaves has been evidenced.