Background: KL-6 is a mucin-like glycoprotein expressed on the surface of alveolar type II cells. Elevated concentrations of KL-6 in serum and epithelial lining fluid (ELF) in patients with acute respiratory distress syndrome (ARDS) have been previously reported; however, kinetics and prognostic significance of KL-6 have not been extensively studied. This study was conducted to clarify these points in ARDS patients. Methods: Thirty-two patients with ARDS who received mechanical ventilation under intubation were studied for 28 days. ELF and blood were obtained from each patient at multiple time points after the diagnosis of ARDS. ELF was collected using a bronchoscopic microsampling procedure, and ELF and serum KL-6 concentrations were measured. Results: KL-6 levels in ELF on days 0 to 3 after ARDS diagnosis were significantly higher in nonsurvivors than in survivors, and thereafter, there was no difference in concentrations between the two groups. Serum KL-6 levels did not show statistically significant differences between nonsurvivors and survivors at any time point. When the highest KL-6 levels in ELF and serum sample from each patient were examined, KL-6 levels in both ELF and serum were significantly higher in nonsurvivors than in survivors. The optimal cut-off values were set at 3453 U/mL for ELF and 530 U/mL for serum by receiver operating characteristic (ROC) curve analyses. Patients with KL-6 concentrations in ELF higher than 3453 U/mL or serum concentrations higher than 530 U/mL had significantly lower survival rates up to 90 days after ARDS diagnosis. Conclusions: ELF and serum KL-6 concentrations were found to be good indicators of clinical outcome in ARDS patients. Particularly, KL-6 levels in ELF measured during the early period after the diagnosis were useful for predicting prognosis in ARDS patients.

Background: Diffuse alveolar hemorrhage syndrome is a life threatening condition with diverse etiologies. Sensitive prognostic markers for diffuse alveolar hemorrhage have not been well investigated. Serum KL-6 is a biomarker for various interstitial lung disease associated with disease activity and prognosis. The purpose of the present study was to evaluate the clinical utility of serum KL-6 level as a prognostic marker for diffuse alveolar hemorrhage.Methods: We retrospectively collected 41 consecutive patients clinically diagnosed as having diffuse alveolar hemorrhage who were admitted to the Intensive Care Unit of Hiroshima University Hospital between 2004 and 2011. Correlation between prognosis and age, sex, laboratory findings including serum KL-6, radiological findings, ventilatory modes or therapeutic regimens were evaluated.Results: Baseline and peak serum KL-6 levels were significantly higher in non-survivors compared with survivors. An increase in KL-6 levels during the initial week was associated with a subsequent deterioration of the oxygenation index. Higher baseline KL-6 levels and higher peak KL-6 levels were strongly correlated with death. With a cut-off level of 700 U/mL for peak KL-6, the sensitivity, specificity and accuracy for non-survival were 75%, 85% and 78%, respectively. In the multivariate analysis, only the peak KL-6 level ≥700 U/ml was an independent poor prognostic factor for diffuse alveolar hemorrhage.Conclusions: Peak serum KL-6 level ≥700 U/ml may become a clinically useful marker of poor prognosis for diffuse alveolar hemorrhage.

The biological effects of low-dose-rate (LDR) radiation exposure in nuclear power plant accidents and medical uses of ionizing radiation (IR), although being a social concern, remain unclear. In this study, we evaluated the effects of LDR-IR on global gene expression in human cells and aimed to clarify the mechanisms. RNA-seq analyses demonstrated that relatively low dose rates of IR modify gene expression levels in TIG-3 cells under normoxic conditions, but those effects were attenuated under hypoxia-mimicking conditions. Gene set enrichment analysis demonstrated that LDR-IR significantly decreased gene expression related to cell division, cell cycle, mitosis, and the Aurora kinase B and FOXM1 pathways. Quantitative RT-PCR confirmed the down-regulation of AURKB and FOXM1 genes in TIG-3 cells with LDR-IR or hypoxia-mimicking treatments without any dose-rate effect. Knock-down experiments suggested that HIF-1α and HIF-2α, as well as DEC1, participated in down-regulation of AURKB and FOXM1 under DFOM treatments, but to a lesser extent under LDR-IR treatment. FACS and microscopic analyses demonstrated that LDR-IR induced G0/G1 arrest and increased micronucleus or chromosome condensation. Finally, MTT assays demonstrated that LDR-IR decreased sensitivity to paclitaxel or barasertib in TIG-3 cells but not in A549 cells. In conclusion, LDR-IR modifies global gene expression and cell cycle control, resulting in a reduction of sensitivity to anti-cancer chemotherapy in non-cancer cells and thus a reduction in untoward effects (GA).

Venoarterial-venous extracorporeal membrane oxygenation (VAV ECMO) configuration is a combined procedure of extracorporeal membrane oxygenation (ECMO). The proportion of cardiac and respiratory support can be controlled by adjusting arterial and venous return. Therefore, VAV ECMO can be applicable as a bridging therapy in the transition from venoarterial (VA) to venovenous (VV) ECMO. We present an 11-year-old girl with chemotherapy-induced myocarditis requiring extracorporeal cardiorespiratory support. She showed progressive hypotension, tachycardia, hyperlactemia, and tachypnea under support of catecholamines. Echocardiography showed severe left ventricular hypokinesis with an ejection fraction of 30 %. She was placed on VA ECMO with a drainage catheter from the right femoral vein (19.5 Fr) and a return catheter to the right femoral artery (16.5 Fr). Extracorporeal circulation was initiated at a blood flow of 2.0 L/min (59 mL/kg/min). On day 31, although cardiac function had improved, persistent pulmonary failure made weaning from VA ECMO difficult. We planned transition from VA ECMO to VAV ECMO to ensure gradual tapering of extracorporeal cardiac support while evaluating cardiopulmonary function. An additional return cannula (13.5 Fr) was inserted from the right internal jugular vein, which was connected to the circuit branch from the original returning cannula. We then gradually shifted the blood from the femoral artery to the right internal jugular vein over 24 h. She was successfully switched from VA to VV ECMO via VAV ECMO. VAV ECMO might be an option in ensuring oxygenation to the coronary circulation and allowing time to adequately evaluate cardiac function during transition from VA to VV ECMO. Further investigations using larger cohorts are necessary to validate the efficacy of VAV ECMO as a bridging therapy in the transition from VA to VV ECMO.

Outcomes of pediatric hepatoblastoma (HBL) have improved, but refractory cases still occur. More effective and safer drugs are needed that are based on molecular mechanisms. A disintegrin and metalloproteases (ADAMs) are expressed with high frequency in various human carcinomas and play an important role in cancer progression. In this study, we analyzed expression of ADAMs in HBL with a cDNA microarray dataset and found that the expression level of ADAM32 is particularly high. To investigate the role of ADAM32 in cancer, forced expression or knockdown experiments were conducted with HepG2 and HBL primary cells. Colony formation, cell migration and invasion, and cell viability were increased in HepG2 expressing ADAM32, whereas knockdown of ADAM32 induced a decrease in these cellular functions. Quantitative RT-PCR demonstrated an association between ADAM32 expression and the expression of genes related to cancer stem cells and epithelial–mesenchymal transition (EMT), suggesting a role of ADAM32 in cancer stemness and EMT. Furthermore, knockdown of ADAM32 increased cisplatin-induced apoptosis, and this effect was attenuated by a caspase-8 inhibitor, suggesting that ADAM32 plays a role in extrinsic apoptosis signaling. We conclude that ADAM32 plays a crucial role in progression of HBL, so it might be a promising molecular target in anticancer therapy.