Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing
BMC CANCER
Authors: Zhao, Yue; He, Jun Ying; Cui, Jun Zhao; Meng, Zi-Qi; Zou, Yue Li; Guo, Xiao Su; Chen, Xin; Wang, Xueliang; Yan, Li-Tian; Han, Wei Xin; Li, Chunyan; Guo, Li; Bu, Hui
Abstract
Background This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM). Methods A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were bioinformatically analyzed by (Database for Annotation, Visualization and Integrated Discovery) DAVID software. Results The most common mutated gene wasTP53(54/62; 87.10%), followed byEGFR(44/62; 70.97%),PTEN(39/62; 62.90%),CDKN2A(32/62; 51.61%),APC(27/62: 43.55%),TET2(27/62; 43.55%),GNAQ(18/62; 29.03%),NOTCH1(17/62; 27.42%),VHL(17/62; 27.42%),FLT3(16/62; 25.81%),PTCH1(15/62; 24.19%),BRCA2(13/62; 20.97%),KDR(10/62; 16.13%),KIT(9/62; 14.52%),MLH1(9/62; 14.52%),ATM(8/62; 12.90%),CBL(8/62; 12.90%), andDNMT3A(7/62; 11.29%). The mutated genes were enriched in the PI3K-Akt signaling pathway by the KEGG pathway analysis. Furthermore, the CNVs of these genes were also identified in these 62 samples. The mutated genes in CSF samples receiving intrathecal chemotherapy and systemic therapy were enriched in the ERK1/2 signaling pathway. Conclusions This study identified genes mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway.
Ameliorative effects of cerebrolysin against isoproterenol-induced myocardial injury in male rats
LIFE SCIENCES
Authors: Ardjmand, Abolfazl; Shahaboddin, Mohammad Esmaeil; Mazoochi, Tahere; Ghavipanjeh, Gholamreza
Abstract
Aims: Myocardial injury (MI) is the principal cause of death from cardiovascular disease (CVD). The present study was conducted to investigate the ameliorative and antioxidant effects of cerebrolysin (CBL) on iso-proterenol-induced MI in rats. Methods: MI was induced in the rats by subcutaneously injecting 100 mg/kg of isoproterenol (ISO) in the first two days. The serum levels of creatine phosphokinase (CK-MB) and cardiac troponin I (cTnI) were measured on the third day to confirm MI. The post-treatment involved intraperitoneally injecting 5 ml/kg of CBL for 7 days. Nitric oxide (NO), malondialdehyde (MDA) in the heart tissue and catalase (CAT) and serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured on the 10th day using the enzyme-linked immunosorbent assay (ELISA). Histopathological examinations of the heart tissue were also performed. Findings: The present results suggested significant increases in CK-MB, cTnI, MDA and NO. A significant decrease was also observed in the ISO-treated rats in certain antioxidant enzymes, including CAT and GPX. CBL administration showed a significant ameliorative increase against the oxidative ISO-induced damage. Moreover, the histopathological findings showed lower levels of the infiltration of inflammatory cells and edema and vascular proliferation in the CBL-treated rats. Significance: The present histopathological and biochemical findings attributed antioxidant properties to CBL in the rat myocardium and suggested protective effects on ISO-induced MI.