Abstract: Melanoma arises from pigment-producing cells called melanocytes located in the basal layers of the epidermis of the skin. Cytoglobin (CYGB) is a ubiquitously expressed hexacoordinated globin that is highly enriched in me­lanocytes and frequently downregulated during melanomagenesis. Previously, we showed that non-thermal plasma (NTP)-produced reactive oxygen and nitrogen species (RONS) lead to the formation of an intra­ molecular disulfide bridge that would allow CYGB to function as a redox-sensitive protein. Here, we investigate the cytotoxic effect of indirect NTP treatment in two melanoma cell lines with divergent endogenous CYGB expression levels, and we explore the role of CYGB in determining treatment outcome. Our findings are consistent with previous studies supporting that NTP cytotoxicity is mediated through the production of RONS and leads to apoptotic cell death in melanoma cells. Furthermore, we show that NTP-treated solutions elicit an antioxidant response through the activation of nuclear factor erythroid 2–related factor 2 (NRF2). The knock­ down and overexpression of CYGB respectively sensitizes and protects melanoma cells from RONS-induced apoptotic cell death. The presence of CYGB enhances heme-oxygenase 1 (HO-1) and NRF2 protein expression levels, whereas the absence impairs their expression. Moreover, analysis of the CYGB-dependent transcriptome demonstrates the tumor suppressor long non-coding RNA maternally expressed 3 (MEG3) as a hitherto unde­ scribed link between CYGB and NRF2. Thus, the presence of CYGB, at least in melanoma cells, seems to play a central role in determining the therapeutic outcome of RONS-inducing anticancer therapies, like NTP-treated solutions, possessing both tumor-suppressive and oncogenic features. Hence, CYGB expression could be of in­ terest either as a biomarker or as a candidate for future targeted therapies in melanoma.

Abstract: Background: Inhaled formulations using extrafine particles of long-acting beta(2)-agonists and corticosteroids were developed to optimize asthma treatment. Findings that these combinations reach and treat smaller airways more effectively are predominantly based on general non-specific outcomes with little information on regional characteristics. Objectives: This study aims to assess long-term effects of extrafine beclomethasone/formoterol on small airways of asthmatic patients using novel functional imaging methods. Methods: Twenty-four stable asthma patients were subdivided into three groups (steroid naive, n = 7; partially controlled, n = 6; well controlled, n = 11). Current treatment was switched to a fixed combination of extrafine beclomethasone/formoterol (Foster (R); Chiesi Pharmaceuticals, Parma, Italy). Patients underwent lung function evaluation and thorax high-resolution computerized tomography (HRCT) scan. Local airway resistance was obtained from computational fluid dynamics (CFD). Results: After 6 months, the entire population showed improvement in pre-bronchodilation imaging parameters, including small airway volume (p = 0.0007), resistance (p = 0.011), and asthma control score (p = 0.016). Changes in small airway volume correlated with changes in asthma control score (p = 0.004). Forced expiratory volume in 1 s (p = 0.044) and exhaled nitric oxide (p = 0.040) also improved. Functional imaging provided more detail and clinical relevance compared to lung function tests, especially in the well-controlled group where only functional imaging parameters showed significant improvement, while the correlation with asthma control score remained. Conclusions: Extrafine beclomethasone/formoterol results in a significant reduction of small airway obstruction, detectable by functional imaging (HRCT/CFD). Changes in imaging parameters correlated significantly with clinically relevant improvements. This indicates that functional imaging is a useful tool for sensitive assessment of changes in the respiratory system after asthma treatment. Copyright (C) 2013 S. Karger AG, Basel

Abstract: Patients with sleep related breathing disorders (SRBD) can be treated with nasal continuous positive airway pressure (nCPAP) or with several upper airway (UA) interventions. While nCPAP is almost always effective when clinically well tolerated, the therapeutic outcome of UA surgery and UA devices is difficult to predict. The improvement of our capability to perform the latter predictions more accurately is of great clinical importance since it will prevent patients to be treated with ineffective, sometimes irreversible, techniques. In this review we describe the importance of new imaging methods in this respect. We first refer to the most important pathophysiological mechanisms known so far to play a role in SRBD, indicating that functional imaging could elucidate these mechanisms in a patient specific manner. Then we describe the new technologies that make UA imaging more functional referring to the data as they are presently available. Finally we summarise the studies that do indicate that the use of functional imaging of the UA in SRBD patients may significantly help to predict the clinical outcome after UA interventions.