Chiara Romei

The A2B Adenosine Receptor Modulates the Epithelial– Mesenchymal Transition through the Balance of cAMP/PKA and MAPK/ERK Pathway Activation in Human Epithelial Lung Cells

The epithelial-mesenchymal transition (EMT) is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A2B adenosine receptor subtype activation, too. However, the relationship between A2BAR and EMT has not been investigated, yet. Herein, the A2BAR characterization was carried out in human epithelial lung cells. Moreover, the effects of receptor activation on EMT were investigated in the absence and presence of transforming growth factor-beta (TGF-β1), which has been known to promote the transition. The A2BAR activation alone decreased and increased the expression of epithelial markers (E-cadherin) and the mesenchymal one (Vimentin, N-cadherin), respectively, nevertheless a complete EMT was not observed. Surprisingly, the receptor activation counteracted the EMT induced by TGF-β1. Several intracellular pathways regulate the EMT: high levels of cAMP and ERK1/2 phosphorylation has been demonstrated to counteract and promote the transition, respectively. The A2BAR stimulation was able to modulated these two pathways, cAMP/PKA and MAPK/ERK, shifting the fine balance toward activation or inhibition of EMT. In fact, using a selective PKA inhibitor, which blocks the cAMP pathway, the A2BAR-mediated EMT promotion were exacerbated, and conversely the selective inhibition of MAPK/ERK counteracted the receptor-induced transition. These results highlighted the A2BAR as one of the receptors involved in the modulation of EMT process. Nevertheless, its activation is not enough to trigger a complete transition, its ability to affect different intracellular pathways could represent a mechanism at the basis of EMT maintenance/inhibition based on the extracellular microenvironment. Despite further investigations are needed, herein for the first time the A2BAR has been related to the EMT process, and therefore to the different EMT-related pathologies.

Evaluation of air photoactivation at linear accelerators for radiotherapy

High-energy x-rays produced by radiotherapy accelerators operating at potentials above 10 MV may activate the air via (γ, n) reactions with both oxygen and nitrogen. While the activation products are relatively short-lived, personnel entering the accelerator room may inhale some radioactive air, which warrants internal dosimetry assessments. This work illustrates a method based on the use of ammonium nitrate solutions for the evaluation of photon-induced air activation and for the estimate of internal doses to radiotherapy personnel. Air activation and internal dosimetry assessments based on our method are presented for some widespread radiotherapy linear accelerator models. Our results indicate that the equivalent dose to the lungs of radiotherapy personnel is negligible for beam energies below 18 MeV.

Development of anthropomorphic hand phantoms for personal dosimetry in 90Y-Zevalin preparation and patient delivering

Anthropomorphic tissue-equivalent hand phantoms were achieved to measure the extremity dose involved in Zevalin (90)Y-labelling and patient delivering procedure for radioimmunotherapy treatment of non-Hodgkin lymphoma. The extremity doses to hands and wrists of operators were measured by using thermoluminescent detectors mounted on the developed phantoms. Measurements of chest- and lens-equivalent doses performed on a Rando phantom are also reported.

Application of the BINS superheated drop detector spectrometer to the 9Be(p,xn) neutron energy spectrum determination

In the framework of TRASCO-BNCT project, a Bubble Interactive Neutron Spectrometer (BINS) device was applied to the characterization of the angle-and energy-differential neutron spectra generated by the 9Be(p,xn)reaction. The BINS spectrometer uses two superheated emulsion detectors, sequentially operated at different temperatures and thus provides a series of six sharp threshold responses, covering the 0.1-10 MeV neutron energy range. Spectrum unfolding of the data was performed by means of MAXED code. The obtained angle, energy-differential spectra were compared with those measured with a Bonner sphere spectrometer, a silicon telescope spectrometer and literature data.

Imaging of malignant pleural mesothelioma: it is possible a screening or early diagnosis program?—a systematic review about the use of screening programs in a population of asbestos exposed workers

Malignant pleural mesothelioma (MPM) in an uncommon neoplasia with high mortality rate, mostly related to professional asbestos exposure. Clinical manifestations are not specific so that diagnosis is performed at advanced stage and screening protocols are not feasible now. On the other hand, asbestos-exposed workers have a high incidence of developing lung cancer. Low-dose computed tomography (LDCT) is a volumetric acquisition technique with high spatial resolution and a low dose exposure; it is used in many trials to detect lung tumours at an early stage in screening protocols, reducing mortality rate in smoker subjects. In recent papers, the possibly role of lung cancer screening was evaluated and recommended also in subjects exposed to asbestos. This article summarizes previous and present clinical trials validated for lung cancer screening, to discuss the possibility of early diagnosis or screening programs in a population of asbestos exposed workers by LDCT.

Analysis of the response of innovative neutron detectors with monoenergetic neutron beams

Various neutron detectors are currently under development at the University of Pisa. The response of these devices is investigated using monoenergetic neutron beams produced at the CN accelerator of INFN Legnaro National Laboratories with thin lithium target bombarded by protons at different energies, exploiting the 7Li(p,n)7Be reaction.