Effect of Cetuximab and EGFR Small Interfering RNA Combination Treatment in NSCLC Cell Lines with Wild Type EGFR and Use of KRAS as a Possible Biomarker for Treatment Responsiveness

[Background] The epidermal growth factor receptor (EGFR) is a therapeutic target for patients with non-small cell lung cancer (NSCLC). Cetuximab is an anti-EGFR monoclonal antibody that inhibits EGFR signaling and proliferation of colorectal cancer and head and neck cancers. Since only few NSCLC patients benefit from cetuximab therapy, we evaluated a novel combination treatment using cetuximab and EGFR small interfering RNA (siRNA) to strongly suppress EGFR signaling and searched for a biomarker in NSCLC cell lines harboring wild-type EGFR. [Methods] Alterations in EGFR and its downstream genes in five NSCLC cell lines (A549, Lu99, 86-2, Sq19 and Ma10) were assessed through sequencing. The protein expression levels of these molecules were assessed through western blotting. The effect of combination treatment was determined through cell proliferation assay, caspase-3/7 assay, invasion assay, and migration assay. [Results] All cell lines were harboring wild-type EGFR, whereas KRAS, PTEN, TP53 and TP53 were mutated in A549 and Lu99; Lu99 and Sq19; Lu99, 86-2, Sq19 and Ma10; and A549, 86-2, and Sq19 cell lines, respectively. PTEN was not expressed in Sq19, and LKB1 was not expressed in both A549 and Sq19. TP53 was not expressed in both A549 and Lu99. The combination of cetuximab and EGFR siRNA significantly suppressed cell proliferation in 86-2, Sq19 and Ma10, which express wild-type KRAS. It induced apoptosis in A549, 86-2 and Ma10 cells, which express wild type PTEN. The combination treatment had no effect either on cell invasion nor migration in all cell lines. [Conclusion] EGFR targeted therapy using the combination of cetuximab and EGFR siRNA is effective in NSCLC cell lines harboring wild-type EGFR. Wild-type KRAS may act as a potential biomarker for response to combination treatment by the induction of apoptosis in cells with wild-type PTEN

Digestibility and gastrointestinal transit of Ulva fasciata seaweed meal in tilapia (Oreochromis niloticus) juveniles: basis for the inclusion of a sustainable ingredient in aquafeeds

The seaweed Ulva fasciata has many features favorable to integrated multi-trophic aquaculture (IMTA). It is efficient at biofiltering, shows high biomass production, and is rich in many nutrients useful in aquatic animal diets. We evaluated the digestibility of the seaweed meal of U. fasciata produced in IMTA and its effects on gastrointestinal transit time in tilapia (Oreochromis niloticus) juveniles. Juveniles (6.30 ± 1.80 g initial weight, and 5.5 ± 0.61 cm initial length) were cultivated in six tanks (50 individuals per tank) in a closed recirculating aquaculture system. The digestibility of Ulva meal was 57.92 ± 5.21% for dry material, 78.59 ± 1.91% for protein, and 69.87 ± 3.72% for energy. The inclusion of 10% seaweed meal did not alter the gastrointestinal transit time in tilapia juveniles as compared to controls. The earliest colored feces were observed four hours after first feeding in both treatments (feed diets with [10%] and without seaweed); all fecal material was colored after ten hours. The digestibility of seaweed meal was satisfactory for dry material, protein, and gross energy, and the inclusion of 10% of that meal did not change gastrointestinal transit time - indicating that the inclusion of 10% seaweed meal in tilapia diet is safe and without any nutritional use losses

Evaluation of antigen-positive toxin-negative enzyme immunoassay results for the diagnosis of toxigenic Clostridium difficile infection

Clostridium difficile (C. difficile)-associated diarrhea (CDAD) is a challenging nosocomial infectious disease. C. DIFF Quik Chek Complete assay is widely used to detect glutamate dehydrogenase (GDH) antigen and toxin A/B of C. difficile simultaneously. However, the interpretation of GDH positive/toxin negative results is problematic.We performed a retrospective study of patients with GDH positive/toxin negative results to determine the probability of detecting toxigenic C. difficile and its risk factors. Between April 2012 and March 2017, we investigated cultures of fecal specimens followed by toxin detection tests. The clinical histories of patients with and without toxigenic C. difficile were compared using univariate- and multivariate-analyses. In total, 2675 patients were examined using C. Diff Quik Chek Complete assay. Among 356 GDH positive/toxin negative patients, cultures were performed in 220 cases and toxigenic C. difficile was recovered from 139 (63.2%) specimens. Patients with toxigenic C. difficile had significantly lower body mass index than those without. Over half the GDH positive/toxin negative patients were infected with toxigenic C. difficile. Lower BMI was a CDAD risk factor in this patient population. These data can be utilized to initiate isolation and clinical interventions before confirmatory test results are available

Health-Related Quality of Life in Patients on Home Oxygen Therapy with Telemonitoring

Home oxygen therapy (HOT) is an important treatment for patients with chronic respiratory diseases. Recently, telemonitoring of HOT has been become available. In the present study, we examined whether telemonitoring of HOT could improve health-related quality of life (HRQOL). Twelve patients receiving HOT participated in this study. The oxygen flow rates, use of the oxygen concentrator, and the values of percutaneous arterial oxygen saturation measured by each patient with a pulse oximeter were checked using a telemonitoring system for a period of one month. Interventions based on the results obtained were carried out in order to optimize oxygen use in this patient cohort. We evaluated the results of the SF-36 questionnaire before the initiation of telemonitoring and at 3 months after completion of the study. We identified significant improvements in SF-36 sub-scores after completion of this intervention. We conclude that telemonitoring may be a useful method to improve HRQOL

Assessing Autonomic Nervous System Function by Pulse Rate Variability in Patients with Chronic Obstructive Pulmonary Disease

Heart rate variability (HRV) is measured to analyze autonomic nervous system function in humans, and pulse rate variability (PRV) assessed using the photoplethysmography method with a pulse oximeter has been proposed as a surrogate for HRV. To examine whether PRV is compatible with HRV in patients with chronic obstructive pulmonary disease (COPD), we simultaneously measured HRV with an electrocardiogram and PRV with a pulse oximeter in patients with COPD, and compared low-frequency and high-frequency components computed from HRV and PRV as indicators of autonomic nervous system function. In a Bland–Altman analysis, the low-frequency component computed from HRV exhibited good consistency with that computed from PRV. The high-frequency component showed a significant fixed error but relatively good consistency. Our results indicate that autonomic nervous system function may be estimated with the low-frequency component by measuring PRV with a pulse oximeter in patients with COPD