Effect of cytidine analogs on cell growth and differentiation on a human neuroblastoma line

The cytidine analog 5-AZA-2'-deoxycytidine (5-AZA-CdR) has been demonstrated to induce cellular differentiation; on the other hand, induction of differentiation has been suggested as a possible form of therapy for leukemic cells. We have evaluated the possibility that the neuroblastoma malignant tumor growth could be controlled by treatment that promotes the differentiation of immature tumor cells. We have previously reported on differentiation of murine neuroblastoma cells (41A3) treated with 5-AZA-CdR. In this paper, we describe the effect of 5-AZA-CdR on human neuroblastoma cell line CHP-100. The drug-treated cells show some degree of differentiation, demonstrated by morphological and biochemical markers. A significant DNA hypomethylation and partial inhibition of DNA synthesis and cell proliferation is also observed. This effect is more stable than that caused by another cytidine analog, Cytosine-beta-D-Arabinofuranoside (ARA-C).     

Recovering mountain Mediterranean grasslands for breeding birds: ecology and population status shape species responses to management

The Mediterranean basin is considered one of the most important biodiversity hotspots. This extraordinary richness originates mainly from thousands of years of human activities that deeply modified the landscape. Safeguarding the so-called cultural landscapes plays a key role in biodiversity conservation. In this paper we present the results of our monitoring of the effects of the life project “Preservation of mountain grasslands of the Tuscan Apennines”, mainly characterized by shrub-cutting actions, on bird populations in the Pratomagno pasture, one of the two areas where the project was implemented, a SPA in eastern Tuscany. The monitoring plan covers a period of 5 years. We tested the effects of shrub clearing on a series of bird community parameters, such as abundance and richness of common species and of some ecological guilds. We also tested the timing of the response to the interventions (immediate or drawn out over time). Our results show a dramatic decrease of birds associated with shrubland, while there were no important increases in grassland species, with the sole exception of Woodlark. Regardless of their positive or negative effects, our results show different response times for individual species or groups of species. Moreover, species with a bad regional conservation status increased less than those with a good one. Broadly speaking, these results suggest that the efficacy of such projects depends on a careful preliminary assessment of a number of aspects, encompassing the nature of the interventions themselves and the characteristics of the target sites, but also the type of response of target species and the conservation status of target populations.     

Survival in different habitats: Extreme ultramafic and calcareous soils affect Stachys recta essential oils composition

Two populations of Stachys recta growing in Italy on ultramafic and calcareous soils have been studied for their essential oils. Although the yields were comparable, the composition of the essential oils differed significantly. Plants growing on ultramafic soil produced mainly non-terpene derivatives (55.7%), of which the most abundant ones were 1-octen-3-ol (38.2%) and (E)-3-hexen-1-ol (5.9%); the terpenes α-cadinol (6.1%) and δ-cadinene (5.6%) were also significantly represented. In contrast, the populations living on calcareous soil produced an essential oil dominated by terpenes (93.8%), with germacrene D (18.8%), β-caryophyllene (17.7%), 1,8-cineole (15.9%) and α-pinene (14.2%) among the main components.     

Routine Clinical-Pathologic Correlation of Pigmented Skin Tumors Can Influence Patient Management

Background

Several studies have demonstrated the benefit of integrating clinical with pathologic information, to obtain a confident diagnosis for melanocytic tumors. However, all those studies were conducted retrospectively and no data are currently available about the role of a clinical-pathologic correlation approach on a daily basis in clinical practice.

Aim of the Study

In our study, we evaluated the impact of a routine clinical-pathologic correlation approach for difficult skin tumors seen over 3 years in a tertiary referral center.

Results

Interestingly, a re-appraisal was requested for 158 out of 2015 (7.7%) excised lesions because clinical-pathologic correlation was missing. Of note, in 0.6% of them (13 out of 2045) the first histologic diagnosis was revised in the light of clinical information that assisted the Pathologist to re-evaluate the histopathologic findings that might be bland or inconspicuous per se.

Conclusion

In conclusion, our study demonstrated that an integrated approach involving clinicians and pathologists allows improving management of selected patients by shifting from a simply disease-focused management (melanoma versus nevus) to a patient-centered approach.     

MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells

Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30–40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation are not sufficient to predict a positive response of NSCLC cells to a cocktail of MET and EGFR inhibitors and highlights the importance of identifying more reliable biomarkers to predict the efficacy of treatments in NSCLC patients resistant to EGFR TKI.