Re-evaluation of the diagnostic value of fractional exhaled nitric oxide & its impact in patients with asthma

Background & objectives: The diagnostic value of fractional exhaled nitric oxide (FeNO) in patients with asthma remains controversial. This study was aimed to re-evaluate the diagnostic value of FeNO in specific groups with asthma and identify potential factors associated with FeNO. Methods: FeNO measurement and bronchial provocation test (BPT) or bronchodilator test (BDT) were performed in patients with suggestive symptoms for asthma. Correlation analysis was performed, and receiver-operating characteristic (ROC) curves and area under the curve (AUC) were calculated to evaluate the accuracy of FeNO in diagnosis. Results: A total of 265 (66.3%) patients with asthma were identified in 400 individuals suspected to have asthma from October 2014 to June 2015. Positive correlations of gender (r=0.138, P=0.005), atopy (r=0.598, P <0.001) and rhinitis (r=0.485, P <0.001) but negative correlations of age (r=?0.220, P <0.001) and the cumulative methacholine dosage with a 20 per cent decrease in forced expiratory volume in one second (r=?0.197, P <0.001) with FeNO were found. AUC of FeNO in whole population and patients with atopy and rhinitis was 0.728 [95% confidence interval (CI) 0.675-0.781, P <0.001] and 0.752 (95% CI 0.640-0.865, P <0.001), while the cut-offs were 23.5 and 44.5 parts per billion (ppb), respectively, rendering sensitivities, specificities, positive predictive value and negative predictive value of 79.9, 54.7, 77.9, 58.1 and 78.7, 67.9, 89.2 and 48.7 per cent, respectively. The cut-off of FeNO with specificity of 90 per cent (FeNO90) for all patients and a sub-group of patients with atopy and rhinitis was 59.5 and 90.5 ppb, respectively, while FeNO90decreased by 12 ppb with every 10 years. Interpretation & conclusions: Our findings show that the diagnostic value of FeNO varies in different groups of patients with asthma, thus, the cut-off point should be adjusted in different asthmatic sub-populations. A cut-off point of FeNO with a specificity >90 per cent could decrease the false-positive rate.

A retrospective clinical study of bevacizumab combined with gemcibabine or paclitaxel in the treatment of recurrent ovarian cancer.

BACKGROUND: Bevacizumab, a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A, was described to be effective in the treatment of recurrent or platinum‑resistance ovarian cancer. The present retrospective study was performed to further evaluate the clinical efficacy and toxicity of bevacizumab in the treatment of Chinese recurrent ovarian cancer patients who had been previously treated by platinum‑based chemotherapy. MATERIALS AND METHODS: We reviewed the hospital database and finally included 26 recurrent ovarian cancer patients who were treated with bevacizumab combined with gemcibabine or paclitaxel or single agent. All included patients received >3 cycle of bevacizumab treatment. The tumor response, overall survival, and toxicities were documented. RESULTS: Under the treatment of bevacizumab combined with gemcibabine or paclitaxel, 2 complete response (7.7%), 8 partial response (30.8%), 7 stable disease (26.9%) and 9 progression disease (34.6%) was documented with the objective response rate of 38.5% and disease control rate of 65.4%. The median overall survival from the first application of bevacizumab was 15.3 months [Figure 1] for all of the 26 patients. The median overall survival time was 16.2 and 14.0 months for bevacizumab + gemcitabine and bevacizumab + paclitaxel treatment schedule respectively. The overall survival was not different between bevacizumab + gemcitabine and bevacizumab + paclitaxel treatment regimen hazard ratio = 0.80 (95% confidence interval: 0.32–2, P = 0.64). The hypertension and proteinuria were the major bevacizumab related toxicities. CONCLUSIONS: Bevacizumab combined with gemcibabine or paclitaxel was a promising treatment schedule for platinum‑resistance recurrent ovarian cancer.

RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway

Angiopoietin (Ang)-1 and Ang-2 interact in angiogenesis to activate the Tie-2 receptor, which may be involved in new vessel maturation and regression. Mast cells (MCs) are also involved in formation of new blood vessels and angiogenesis. The present study was designed to test whether MCs can mediate angiogenesis in myocardial microvascular endothelial cells (MMVECs). Using a rat MMVEC and MC co-culture system, we observed that Ang-1 protein levels were very low even though its mRNA levels were increased by MCs. Interestingly, MCs were able to enhance migration, proliferation, and capillary-like tube formation, which were associated with suppressed Ang-2 protein expression, but not Tie-2 expression levels. These MCs induced effects that could be reversed by either tryptase inhibitor [N-tosyl-L-lysine chloromethyl ketone (TLCK)] or chymase inhibitor (N-tosyl-L-phenylalanyl chloromethyl ketone), with TLCK showing greater effects. In conclusion, our data indicated that MCs can interrupt neovessel maturation via suppression of the Ang-2/Tie-2 signaling pathway.