Use of cell free DNA as a prognostic biomarker in non-small cell lung cancer patients with bone metastasis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is difficult to treat when metastasis has occurred. This study explores the use of cell-free DNA in the clinical management of NSCLC patients who have Kirsten rat sarcoma viral oncogene homolog (KRAS)-positive mutations and as a marker for prognosis. METHODS: Peripheral blood collected from advanced NSCLC patients was examined with digital droplet polymerase chain reaction and ultraviolet spectrometry. KRAS mutations were analyzed and quantitated. The specificity and sensitivity of the proposed assay was computed by associating the results with tumor tissue specimens. Comparison against different sub-groups of patients with different metastatic sites and healthy volunteers were made. Patients were subsequently followed up and survival analysis was conducted. RESULTS: Among the 186 patients recruited, 150 had concordant KRAS mutational profiles using cell-free DNA with tumor tissues. The assay sensitivity and specificity were 80.6% and 100%, respectively. For the 150 patients with concordant results, the range of cell-free DNA quantities in peripheral blood was 5.3 to 115 ng. Among the patient groups with different metastatic sites, we observed that patients with bone metastasis had higher concentrations of cell-free DNA. Survival analysis showed that these patients had worse survival outcome. Patients with higher KRAS counts in peripheral blood also had worse outcome. CONCLUSION: The use of cell-free DNA presents opportunities for risk stratification of patients and possibly aids in the clinical management of the disease. In the current study for NSCLC, patients with bone metastases showed higher cell-free DNA concentrations. Quantitating the concentrations of cell-free DNA presents a noninvasive biomarker capable of prognostic utility.

[Study on the mechanism of protective effect of oral L-arginine on intestine after scald injury in rats].

OBJECTIVE: To explore the mechanism of protective effect of oral L-arginine (L-Arg) on the intestine after scald injury in rats. METHODS: Sixty-six Sprague-Dawley (SD) rats were randomly divided into three groups: i.e. normal control (N, n = 6, without treatment), oral L-arginine group (A, n = 30, with 1 ml 70 g/L of L-Arg per os 2 times a day from 2 post scald hour (PSH)) on with normal enteral feeding and group B (n = 30, with oral feeding of cold boiled water after scald). The changes in the content of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), endothelin (ET), ET/NO ratio in the intestine and the level of plasma endotoxin (LPS) in portal vein were assessed at 6, 12, 24, 48, 72 PSH. Ileum tissue samples were harvested for pathological examination. RESULTS: The ET content in the intestinal tissue in A group at 6, 12 and 24 PSH (0.80 +/- 0.26 ng/g, 0.75 +/- 0.30 ng/g, 0.63 +/- 0.22 ng/g) was obviously lower than that in B group (1.26 +/- 0.38 ng/g, 1.34 +/- 0.37 ng/g, 0.97 +/- 0.19 ng/g, P < 0.05), but the NO contents in the intestine in A group at the same time points were significantly higher than that in B group (P < 0.01). The ET/NO ratio and the level of plasma endotoxin in A group were significantly lower than those in B group at each time point (P < 0.05 or 0.01). Pathological examination showed that the intestinal mucosal injury in the A group was obviously milder than that in the B group. CONCLUSION: Oral L-arginine was shown to have the effects to ameliorate ischemia reperfusion injury of the intestine and to protect the barrier function of the intestinal mucosa. This might be related to an increase in the NO level in intestinal mucosa resulting in maintenance of a stable ET/NO ratio.