cyclic-gmp and Carcinoma--Non-Small-Cell-Lung

Since the function of microRNA (miR)-210 in non-small cell lung cancer (NSCLC) remains unclear, we aimed to explore the clinical significance of miR-210 in NSCLC.. NSCLC-related data from 1673 samples on Gene Expression Omnibus and 1090 samples on The Cancer Genome Atlas were obtained and analyzed. The expression level of miR-210 was validated via real-time quantitative PCR analysis with 125 paired clinical samples. A meta-analysis was performed to generate a comprehensive understanding of miR-210 expression and its clinical significance in NSCLC. In addition, bioinformatics analysis was also conducted to reveal the potential underlying mechanism of miR-210 action in NSCLC.. miR-210 expression was consistently elevated in NSCLC solid tissue samples. However, its expression was controversial in easily obtained body fluids (i.e., blood, plasma, and serum). Moreover, an overall pooled meta-analysis implied a comparatively higher level of miR-210 expression in NSCLC cancerous tissue than in normal control tissue (P < 0.001). In addition, a meta-analysis of outcome revealed a significant diagnostic capacity of miR-210 in NSCLC by detecting its expression in serum and sputum (area under the summary receiver operating characteristic curve 0.82 and 0.81, respectively). miR-210 overexpression was associated with poor progression-free survival (PFS) in NSCLC and was negatively related to overall survival and disease-free survival. Bioinformatic gene enrichment and annotation analyses showed that the target genes of miR-210 were greatly enriched in cell adhesion and plasma membrane, and three pathways were considered to be the main functional circuits of miR-210: renin secretion, the cGMP-PKG signaling pathway, and cell adhesion molecules.. In NSCLC, miR-210 expression was elevated and overexpression indicated poor PFS. Expression level of miR-210 in serum and sputum showed significant diagnostic value for NSCLC.

Topics: Area Under Curve; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cell Adhesion Molecules; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Databases, Genetic; Disease-Free Survival; Humans; Lung Neoplasms; MicroRNAs; Prognosis; Renin; ROC Curve; Signal Transduction; Sputum; Survival Rate

One-third of patients with lung cancer and hyponatremia have no evidence of ectopic arginine vasopressin (AVP) production and the cause of their hyponatremia is not conclusively established. We sought to distinguish patients with hyponatremia caused by elevated AVP versus those with ectopic atrial natriuretic peptide (ANP) via this detailed metabolic study.. We enrolled 24 patients recently diagnosed with lung cancer in a metabolic study in which patients were placed on sodium and fluid restriction for 4 days. Serum electrolytes, osmolality, urine electrolytes and osmolality, plasma AVP, ANP, aldosterone, urinary cyclic AMP and cyclic guanosine 3',5'-monophosphate were measured daily and tumor tissue was obtained to measure ectopic hormone production. We attempted to characterize the pathophysiology of hyponatremia caused by ectopic ANP production in patients with small cell lung cancer (SCLC) and to determine its effect on the aldosterone axis.. Seven of the nine patients with SCLC presented with hyponatremia and three had elevated ANP levels at presentation without elevation of AVP. All three patients who presented with hyponatremia and elevated ANP showed a decline in serum sodium following fluid restriction, whereas two patients with SCLC and elevated AVP had normalized serum sodium levels. The combination of hyponatremia and elevated ANP was associated with a persistent natriuresis and inappropriately low aldosterone levels despite sodium restriction, suggesting ANP suppression of the aldosterone axis.. Management of patients with hyponatremia and SCLC should be guided by the knowledge that some patients with SCLC have ectopic production of ANP as the cause of their hyponatremia.

Topics: Adult; Aged; Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cyclic AMP; Cyclic GMP; Female; Humans; Hyponatremia; Lung Neoplasms; Male; Middle Aged

Tumor cell migration is considered as a major event in the metastatic cascade. Here we examined the effect of grape seed proanthocyanidins (GSPs) on migration capacity and signaling mechanisms using nonsmall cell human lung cancer cells. Using in vitro migration assay, we found that treatment of A549 and H1299 cells with GSPs resulted in concentration-dependent inhibition of migration of these cells. The migration capacity of cells was reduced in presence of N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. GSPs suppressed the elevated levels of endogenous NO/NOS in A549 and H1299 cells and blocked the migration promoting capacity of L-arginine. Treatment with guanylate cyclase (GC) inhibitor 1-H-[1,2,4]oxadiaxolo[4,3-a]quinolalin-1-one (ODQ) reduced the migration of A549 cells whereas additional presence of 8-bromoguanosine 3'5'-cyclic monophosphate (8-Br-cGMP, cGMP analogue) restored the migration of these cells, suggesting a role for GC in migration of A549 cells. GSPs reduced the elevated levels of cGMP in cancer cells and also blocked the migration restoring activity of 8-Br-cGMP. The mitogen-activated protein kinase kinase (MAPKK) inhibitor, UO126, inhibited the migration of A549 cells, indicating a role for MAPKK in the migration. Additionally, UO126 and ODQ inhibited the migration restoring effects of L-arginine in L-NAME-treated cells, suggesting the involvement of cGMP and MAPK pathways in NO-mediated migration. GSPs inhibited L-arginine and 8-Br-cGMP-induced activation of ERK1/2 in A549 cells. Together, these results indicate sequential inhibition of NO/NOS, GC, and MAPK pathways by GSPs in mediating the inhibitory signals for cell migration, an essential step in invasion and metastasis.

Topics: Adenocarcinoma; Blotting, Western; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Cell Movement; Cell Proliferation; Cell Survival; Cyclic GMP; Enzyme Inhibitors; Fluorescent Antibody Technique; Grape Seed Extract; Guanylate Cyclase; Humans; Lung Neoplasms; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxadiazoles; Plant Extracts; Proanthocyanidins; Quinoxalines; Receptors, Cell Surface; Signal Transduction; Tumor Cells, Cultured; Vitis