Larval crowding results in hormesis-like effects on longevity in Drosophila: timing of eclosion as a model.

There is increasing evidence that stress during development can affect adult-life health status and longevity. In the present study, we examined life span (LS), fly weight, fecundity and expression levels of longevity-associated genes (Hsp70, InR, dSir2, dTOR and dFOXO) in adult Drosophila melanogaster flies reared in normal [low density (LD), ~ 300-400 eggs per jar] or crowded [high density (HD), more than 3000 eggs per jar] conditions by using the order (day) of emergence as an index of the developmental duration (HD1-5 groups). Developmental time showed a significant trend to increase while weight showed a significant trend to decrease with increasing the timing of emergence. In both males and females eclosed during first 2 days in HD conditions (HD1 and HD2 groups), both mean and maximum LSs were significantly increased in comparison to LD group. In males, mean LS was increased by 24.0% and 23.5% in HD1 and HD2 groups, respectively. In females, corresponding increments in mean LS were 23.8% (HD1 group) and 29.3% (HD2 group). In HD groups, a strong negative association with developmental time has been found for both male and female mean and male maximum LSs; no association with growth rate was observed for female maximum LS. The female reproductive activity (fecundity) tended to decrease with subsequent days of eclosion. In HD groups, the levels of expression of all studied longevity-associated genes tended to increase with the timing of eclosion in males; no differences were observed in females. On the basis of findings obtained, it can be assumed that the development in conditions of larval overpopulation (if not too extended) could trigger hormetic response thereby extending the longevity. Further studies are, however, needed to confirm this assumption.

Prognostic significance of MDM2 gene expression in childhood neuroblastoma.

AIM: To investigate the association of MDM2 expression at the mRNA levels in neuroblastoma with clinical features and unfavorable disease factors to determine the possibility of it usage as a prognostic marker of neuroblastoma. MATERIALS AND METHODS: Total RNA and DNA were extracted from tumor tissue samples of total 91 neuroblastoma patients (mean age: 39.45 ± 4.81 months). MDM2 mRNA levels were detected with Q-PCR. TP53 gene deletion was detected with FISH method. MYCN amplification was detected with -Q-PCR analysis in fresh tumor samples and FISH in FFPE samples. RESULTS: We investigated the association of MDM2 mRNA expression with clinical outcome in neuroblastoma patients (n = 91). Kaplan - Meier curves showed a significant association of high MDM2 expression with poor event-free survival (p < 0.001). Clinical outcome of patients without MYCN amplification with low MDM2 expression was associated with better event-free survival than with high MDM2 expression (p < 0.001). Overexpression of MDM2 can be used as significant prognostic marker for patient stratification on risk groups and treatment optimization. CONCLUSION: Our results showed that the high expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis. It may be a valuable additional molecular marker in guiding specific therapy in MYCN non-amplified NB patients without TP53 gene deletion.