atrial-natriuretic-factor and Small-Cell-Lung-Carcinoma

Hyponatremia is one of the most frequently encountered electrolyte disorder in small cell lung cancer (SCLC) patients. It was shown that some SCLC cell lines could produce atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). The aim of the study was to assess the secretion of ANP, AVP and their relative contributions to hyponatremia in SCLC patients, especially in patients with brain metastases.. In total, 194 SCLC patients including 51 patients with brain metastases were collected. The levels of ANP and AVP were measured with radioimmunoassay kits. And then their associations with serum sodium were investigated. The progression-free survival (PFS) was compared between the hyponatremia group and the normal serum sodium group.. Serum sodium was negatively correlated with the plasma levels of ANP (r=-0.171, p=0.017) and AVP (r = -0.244, p=0.001) in all SCLC patients. In the brain metastatic subgroup, there was also a negative correlation between serum sodium and ANP (r=-0.399, p=0.004), while there was no correlation between serum sodium and AVP (r=-0.232, p=0.101). The occurrence rate of hyponatremia (serum sodium values below 135 mmol/l) in patients with brain metastases (21/51, 41.18%) was higher than that in patients without brain metastases (37/143, 25.87%) (p=0.040). The progression-free survival (PFS) in the hyponatremia group was significantly shorter than that in patients of the group without hyponatremia (p=0.010). Moreover, compared with patients which regained normal serum sodium after the treatment, the PFS of patients still with hyponatremia after the treatment was significantly shorter (p=0.049).. ANP might play a leading role in the formation of hyponatremia of SCLC patients with brain metastases. Correcting hyponatremia timely and appropriately could improve SCLC patients' prognosis.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Brain Neoplasms; Disease-Free Survival; Female; Humans; Hyponatremia; Male; Middle Aged; Prognosis; Radioimmunoassay; Small Cell Lung Carcinoma; Sodium; Survival Analysis

Vascular endothelial growth factor (VEGF) helps control tumour growth via causing new capillaries growth in tumours. Four cardiac hormones [i.e. vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide (KP) and atrial natriuretic peptide (ANP)] that eliminate up to up to 86% of human small-cell lung cancers growing in mice were investigated for their effects on VEGF and the VEGFR2/KDR/Flk-1 receptor. The VEGFR2 receptor is the main receptor mediating VEGF's cancer-enhancing effects.. Four cardiac hormones were evaluated for their ability to decrease VEGF/VEGFR2 measured by ELISAs in three human cancer cell lines.. Vessel dilator, LANP, KP and ANP, over a concentration range of 100 pM to 10 μM, maximally decreased the VEGFR2 receptor in human pancreatic adenocarcinoma cells by 48%, 49%, 74% and 83%. Vessel dilator, LANP, KP and ANP decreased the VEGFR2 receptor by 77%, 89%, 88% and 67% in human small-cell lung cancer cells and by 48%, 92%, 64% and 71% in human prostate cancer cells. These results were confirmed with the cardiac hormones also decreasing the VEGFR2 receptor measured by Western blots. VEGF itself in pancreatic carcinoma cells was decreased by 42%, 58%, 36% and 40% by vessel dilator, LANP, KP and ANP. VEGF levels were decreased 25%, 23%, 17% and 23% in small-cell lung cancer cells and decreased by 24%, 20%, 23% and 24% in prostate cancer cells by vessel dilator, LANP, KP and ANP.. Four cardiac hormones are the first dual inhibitors of VEGF and the VEGFR2/KDR/Flk-1 receptor.

Topics: Angiogenesis Inhibitors; Atrial Natriuretic Factor; Blotting, Western; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Humans; Lung Neoplasms; Male; MAP Kinase Signaling System; Neoplasm Transplantation; Pancreatic Neoplasms; Peptide Fragments; Prostatic Neoplasms; Protein Precursors; Small Cell Lung Carcinoma; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Signal transducers and activators of transcription (STATs) are the final "switches" that activate gene expression patterns that lead to human malignancy. Extracellular signal-regulated kinases (ERK 1/2) activate STAT 3; four cardiovascular hormones inhibit ERK 1/2 kinases, leading to the hypothesis that they may also inhibit STATs. These four cardiac hormones, i.e., vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP), eliminate human cancers growing in mice. These four cardiac hormones' effects on STATs 1 and 3 were examined in human small-cell lung cancer and human pancreatic adenocarcinoma cells. Vessel dilator, LANP, kaliuretic peptide, and ANP maximally decreased STAT 3 by 88, 54, 55, and 65 %, respectively, at their 1 μM concentrations in human small-cell lung cancer cells and STAT 3 by 66, 57, 70, and 77 % in human pancreatic adenocarcinoma cells, respectively. The cardiac hormones (except LANP) also significantly decreased STAT 3 measured by Western blots. These cardiac hormones did not decrease STAT 1 in either human small-cell lung cancer or pancreatic adenocarcinoma cells. We conclude that these four cardiac hormones are significant inhibitors of STAT 3, but not STAT 1, in human small-cell lung cancer and pancreatic adenocarcinoma cells, which suggests a specificity for these hormones' anticancer mechanism(s) of action enzymology in human cancer cells.

Topics: Adenocarcinoma; Atrial Natriuretic Factor; Blotting, Western; Cell Line, Tumor; Humans; Lung Neoplasms; Pancreatic Neoplasms; Peptide Fragments; Protein Precursors; Small Cell Lung Carcinoma; STAT1 Transcription Factor; STAT3 Transcription Factor