Growth and Viability of Cutaneous Squamous Cell Carcinoma Cell Lines Display Different Sensitivities to Isoform-Specific Phosphoinositide 3-Kinase Inhibitors.

Cutaneous squamous cell carcinomas (cSCCs) account for about 20% of keratinocyte carcinomas, the most common cancer in the UK. Therapeutic options for cSCC patients who develop metastasis are limited and a better understanding of the biochemical pathways involved in cSCC development/progression is crucial to identify novel therapeutic targets. Evidence indicates that the phosphoinositide 3-kinases (PI3Ks)/Akt pathway plays an important role, in particular in advanced cSCC. Questions remain of whether all four PI3K isoforms able to activate Akt are involved and whether selective inhibition of specific isoform(s) might represent a more targeted strategy. Here we determined the sensitivity of four patient-derived cSCC cell lines to isoform-specific PI3K inhibitors to start investigating their potential therapeutic value in cSCC. Parallel experiments were performed in immortalized keratinocyte cell lines. We observed that pan PI3Ks inhibition reduced the growth/viability of all tested cell lines, confirming the crucial role of this pathway. Selective inhibition of the PI3K isoform p110α reduced growth/viability of keratinocytes and of two cSCC cell lines while affecting the other two only slightly. Importantly, p110α inhibition reduced Akt phosphorylation in all cSCC cell lines. These data indicate that growth and viability of the investigated cSCC cells display differential sensitivity to isoform-specific PI3K inhibitors.

The effects of long-term exposure to a 2450 MHz electromagnetic field on growth and pubertal development in female Wistar rats.

The aim of this study was to investigate the effects of a 2450 MHz electromagnetic field (EMF) (wireless internet frequency) on the growth and development of female Wistar rats. The study was conducted on three groups of rats. The prenatal and postnatal groups were exposed to EMF 1 h/day beginning from intrauterine and postnatal periods, respectively. The third group was the sham-exposed group. Growth, nutrition and vaginal opening (VO) were regularly monitored. Serum and tissue specimens were collected at puberty. Histological examinations, total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) measurements in ovary and brain tissues and also immunohistochemical staining of the hypothalamus were performed besides the determination of serum FSH, LH, E2 and IGF-1 values. Birth masses of the groups were similar (p > 0.05). Mass gain per day was significantly lower and the puberty was significantly later in the prenatal group. Brain and ovary TOS and OSI values in the prenatal group were significantly increased (p < 0.05) compared to the control group. Serum LH levels of the prenatal and postnatal groups were increased, although serum FSH, and E2 values did not differ among the groups (p > 0.05). Histological examinations of the specimens revealed no statistically significant difference between the groups (p > 0.05). Exposure to 2450 MHz EMF, particularly in the prenatal period, resulted in postnatal growth restriction and delayed puberty in female Wistar rats. Increased TOS and OSI values in the brain and ovary tissues can be interpreted as a sign of chronic stress induced by EMF. This is the first longitudinal study which investigates the effects of EMF induced by wireless internet on pubertal development beside growth.