Unique genomic alterations of cerebrospinal fluid cell-free DNA are critical for targeted therapy of non-small cell lung cancer with leptomeningeal metastasis.

We reported unique molecular features of cerebrospinal fluid (CSF) of NSCLC patients with leptomeningeal metastasis (LM), suggesting to establish CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma and CSF from 131 NSCLC patients with LM, and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors. ALK translocation was detected in 8.3% of tumor tissues, but only 2.4% in CSF and 2.7% in plasma. Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues, but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF may represent better liquid biopsy for NSCLC patients with LM.

[Response of Nostoc flageliforme cell to Cu2+, Cr2+ and Pb2+ stress].

OBJECTIVE: This study aimed to investigate the effects of Cu2+, Cr2+ and Pb2+ stress on Nostoc flagelliforme cell. METHODS: The response of Nostoc flagelliforme cell was analyzed under the stress. The modified BG11 culture medium containing different heavy metal ions of 0, 0.1, 1.0, 10, 100 mg/L was used to cultivate Nostoc flagelliforme cell at 25 degrees C and light intensity of 80 micromol/(m x s). Electrolyte leakage, the activities of superoxide dismutase, the content of malondialdehyde, proline, soluble protein and trehalose were analyzed. RESULTS: Under 1 - 100 mg/L Cu2+, Cr2+ and Pb2+ stress, electrolyte leakage and malondialdehyde contents in Nostoc flagelliforme cell were higher than those in the control group during heavy metal ions stress. Meanwhile, superoxide dismutase activity increased slightly under 10 mg/L, but was lower afterwards. The contents of proline, soluble protein and trehalose increased under 10 mg/L heavy metal ions stress, while declined under extreme heavy metal ions stress (100 mg/L). CONCLUSION: Nostoc flagelliforme cell has resistance to low heavy metal ions stress, but is damaged badly under extreme heavy metal ions stress.

Unique Genomic Alterations of Cerebrospinal Fluid Cell-Free DNA Are Critical for Targeted Therapy of Non-Small Cell Lung Cancer With Leptomeningeal Metastasis.

We reported unique molecular features of cerebrospinal fluid (CSF) of nonsmall cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM), suggesting establishing CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma, and CSF from 131 NSCLC patients with LM and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors. ALK translocation was detected in 8.3% of tumor tissues but only 2.4% in CSF and 2.7% in plasma. Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF might represent better liquid biopsy for NSCLC patients with LM.

Down-regulation of long non-coding RNA AFAP1-AS1 inhibits tumor cell growth and invasion in lung adenocarcinoma.

An increasing number of deregulated long non-coding RNAs (lncRNA) have been implicated in cancer in humans, suggesting that lncRNAs may be involved in tumorigenesis or tumor progression. In previous investigations, lncRNA, AFAP1-AS1 has been found to be associated with several cancers, including nasopharyngeal carcinoma, lung cancer and esophageal adenocarcinoma. However, the function of AFAP1-AS1 in lung cancer has not been reported. In our present study, we found that AFAP1-AS1 was overexpressed in lung adenocarcinoma and associated with survival time. The low expression of AFAP1-AS1 was an independent predictor for disease-free survival in patients with lung adenocarcinoma. Additionally, we transfected AFAP1-AS1 siRNA into H1975 and HCC827, both lung adenocarcinoma cancer cells, and found that cell growth was suppressed, apoptosis induced and invasion inhibited. Taken together, AFAP1-AS1 down-regulation exerts growth suppression and apoptosis induction in lung adenocarcinoma cells, suggested it may participate in turmorigenesis and be a therapeutic target for treating lung adenocarcinoma in future.

Effect of matrine on Kupffer cell activation in cold ischemia reperfusion injury of rat liver.

AIM: To study the effect of matrine on activation of Kupffer cell during cold ischemia and reperfusion injury in rat orthotopic liver transplantation (OLT). METHODS: 168 syngeneic SD rats were randomly divided into four groups: untreated group, small-dose treated group, large-dose treated group and sham operation group. After 5 hours of preservation in Ringer's (LR) solution, orthotopic implantation of the donor liver was performed. At 1 h, 2 h, 4 h and 24 h after reperfusion of the portal vein, 6 rats were killed in each group to collect the serum and the liver for assay and pathology. RESULTS: Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). TNF cytotoxicity level at 2 h decreased significantly by matrine treatment (7.94+/-0.42, 2.39+/-0.19 and 2.01+/-0.13 U/ml, respectively; P<0.01), so did the other three time points. The level of hylluronic acid (HA) and alanine transaminase (ALT) decreased significantly in both treated groups, and matrine treatment markedly ameliorated focal necrosis of hepatocytes, inflammatory cells aggregating, rounding and detachment of sinusoidal endothelial cells (SEC). And no significant difference was observed between the treated groups. CONCLUSION: Matrine can inhibit the activation of Kupffer cell and prevent the donor liver from cold preservation and reperfusion injury in rat orthotopic liver transplantation.

Matrine protects sinusoidal endothelial cells from cold ischemia and reperfusion injury in rat orthotopic liver transplantation.

The effect of matrine on cold ischemia and reperfusion injury of sinusoidal endothelial cells (SEC) was investigated in rats using an orthotopic liver transplantation (OLT) model. Syngeneic Sprague-Dawley (SD) rats were randomly assigned to 4 groups of 32 rats: untreated group (controls), low-dose treated group, high-dose treated group, and sham operation group (normals). After 5 hr of preservation in Ringer's solution, orthotopic implantation of the donor liver was performed. At 1, 2, 4, and 24 hr after reperfusion, 6 rats from each group were killed to collect blood and to excise the median hepatic lobe; the other 8 rats were observed to assess the 1-wk survival rate post-transplantation. All transplant recipients in the untreated group (controls) died within 48 hr, mostly between 10 to 20 hr. Matrine treatment increased the 1-wk survival rate to 75% in both treated groups. Plasma levels of hyaluronic acid (HA) at 1, 2, and 4 hr post-implantation were decreased significantly by matrine treatment. The immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in rat liver decreased significantly in both treated groups, and the pathological changes of SEC were ameliorated. Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). Hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were improved by matrine administration. In conclusion, matrine can protect SEC from cold ischemia and reperfusion injury after rat orthotopic liver transplantation.

Effect of matrine on cold ischemia and reperfusion injury of sinusoidal endothelial cells in rat orthotopic liver transplantation.

AIM: To study the mechanism and prevention of matrine (Mat) on cold ischemia/reperfusion injury of sinusoidal endothelial cells (SEC) in rat orthotopic liver transplantation (OLT). METHODS: One hundred and twenty-six syngeneic SD rats were randomly divided into four groups (n=18): untreated group, 40 mg/kg treated group, 80 mg/kg treated group, and pseudo-treated group. After 5 h of preservation in Ringer's (LR) solution, orthotopic implantation of the donor liver was performed. At 1, 2, and 4 h after reperfusion of the portal vein, 6 rats were killed in each group to collect the serum and the median lobe of liver for assay. RESULTS: The level of hylluronic acid (HA) and intercellular adhesion molecule-1 (ICAM-1) decreased significantly in both treated groups at different times post-transplantation, and their pathological changes of SEC were ameliorated, too. CONCLUSION: Matrine can prevent SEC from ischemia and reperfusion injury in rat orthotopic liver transplantation.