Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is the third prevalent cancer worldwide, the morbidity and mortality of which have been increasing in recent years. As molecular targeting agents, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (McAbs) have significantly increased the progression-free survival (PFS) and overall survival (OS) of metastatic CRC (mCRC) patients. Nevertheless, most patients are eventually resistant to anti-EGFR McAbs. With the intensive study of the mechanism of anti-EGFR drug resistance, a variety of biomarkers and pathways have been found to participate in CRC resistance to anti-EGFR therapy. More and more studies have implicated non-coding RNAs (ncRNAs) primarily including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely involved in tumorigenesis and tumor progression. They function as essential regulators controlling the expression and function of oncogenes. Increasing data have shown ncRNAs affect the resistance of molecular targeted drugs in CRC including anti-EGFR McAbs. In this paper, we have reviewed the advance in mechanisms of ncRNAs in regulating anti-EGFR McAbs therapy resistance in CRC. It provides insight into exploring ncRNAs as new molecular targets and prognostic markers for CRC.

Effects of positive end-expiratory pressure, inhaled nitric oxide and surfactant on expression of proinflammatory cytokines and growth factors in preterm piglet lungs.

We hypothesized that imbalance of proinflammatory cytokines and growth factors (GFs) in immature lungs of early postnatal life may be affected by protective ventilation strategy, and evaluated correlations of these aspects. Preterm neonate piglets were mechanically ventilated with low tidal volume and 5-6 or 10-12 cm H2O positive end-expiratory pressure (PEEP) with or without surfactant and inhaled nitric oxide (iNO) for 6 h, followed by biochemical, biophysical, and histopathological assessment of lung injury severity. Compared with surfactant and the control, iNO combined with lower PEEP exerted better oxygenation, lower activity of myeloperoxidase, lower expression of mRNA of interleukin (IL)-1beta, IL-6, IL-8, and platelet derived growth factor-B (PDGF-B), but higher expression of insulin-like growth factor-I (IGF-I), whereas that of tumor necrosis factor-alpha, keratinocyte GF, hepatocyte GF, vascular endothelial growth factor, and TGF-beta1 had no or modest changes. IL-1beta, IL-6 mRNA were closely correlated to PDGF-B mRNA and myeloperoxidase, but inversely to IGF-I mRNA, Pao2/FiO2 and dynamic lung compliance at 6 h. These results indicate that the association of lower PEEP and iNO may be more protective than surfactant on preventing lung injury and facilitating reparation by affecting the expression of proinflammatory cytokines and GFs.

Effects of hyaluronan-fortified surfactant in ventilated premature piglets with respiratory distress.

We hypothesized that enriching surfactant with hyaluronan would restore lung function when tested in a premature animal model. Newborn piglets (85% gestation, term 112-114 days) were delivered by cesarean section, subjected to mechanical ventilation (tidal volume 6- 8 ml/kg) and randomly assigned to treatment with 50 or 100 mg/kg Curosurf (C50 and C100), 50 or 100 mg/kg Curosurf mixed with 2.5% HA (w/w, CH50 and CH100). A ventilated and not treated group (Cont) and a not treated and not ventilated group (Non) were included as controls. Six hours after treatment the lungs were removed and biochemical, biophysical, cytological and histological analyses were carried out. The CH100, CH50, C100 and C50 groups had variable but significantly improved alveolar phospholipid content, minimal surface tension, alveolar aeration and wet/dry lung weight ratios, but little histological evidence of lung injury. CH100, CH50 and C100 groups had the best effects in terms of oxygenation, lung compliance and histology and evidence of decreased inflammation (IL-8 and TNF-alpha mRNA expression). We conclude that HA added to 50 mg/kg Curosurf or use of 100 mg/kg Curosurf with or without HA provides the best effects in terms of lung function and reduction of inflammation.