atrial-natriuretic-factor and Lung-Neoplasms

The term paraneoplastic syndrome refers to the ability of some tumors to produce signs and symptoms at a distance from the site of the primary tumor or its metastases. Paraneoplastic syndromes may develop before the diagnosis of carcinoma is made. Paraneoplastic syndromes associated with small cell lung cancer (SCLC) include endocrinologic abnormalities secondary to peptide hormone production, and neurologic sequelae due to autoantibody production. This article reviews the common paraneoplastic syndromes that may occur in patients with SCLC.

Topics: ACTH Syndrome, Ectopic; Atrial Natriuretic Factor; Carcinoma, Small Cell; Cerebellar Diseases; Encephalomyelitis; Humans; Inappropriate ADH Syndrome; Lambert-Eaton Myasthenic Syndrome; Lung Neoplasms; Paraneoplastic Syndromes; Retinal Diseases

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Humans; Hyponatremia; Lung Neoplasms; Neoplasms

Postoperative cancer recurrence is a major problem following curative surgery. In a previous retrospective study of lung cancer surgery, we reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduced postoperative recurrence. We demonstrated that ANP inhibited the adhesion of cancer cells to vascular endothelium as a vasoprotective action. The objective of this study is to evaluate the effects of ANP on the incidence of postoperative cancer recurrence in lung cancer surgery.. The present study is a multicenter, randomized trial with two parallel groups of patients with lung cancer comparing surgery alone and surgery with ANP administration for 3 days during the perioperative period. A total of 500 patients will be enrolled from 10 Japanese institutions. The primary endpoint is 2-year relapse-free survival (RFS). The secondary endpoints are 2-year cancer-specific RFS, 5-year RFS, overall survival, the incidence of postoperative complications, and the completion rate of ANP treatment.. The principal question addressed in this trial is whether ANP with its vasoprotective action can reduce cancer recurrence following lung cancer surgery.. UMIN Clinical Trials Registry identifier: UMIN000018480 . Registered on 31 July 2015.

Topics: Antineoplastic Agents; Atrial Natriuretic Factor; Chemotherapy, Adjuvant; Clinical Protocols; Disease-Free Survival; Humans; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Neoplasm Recurrence, Local; Pneumonectomy; Proportional Hazards Models; Research Design; Risk Factors; Time Factors; Treatment Outcome

We previously reported that patients with preoperative B-type natriuretic peptide levels of 30 pg/mL or more have increased risk of postoperative atrial fibrillation after pulmonary resection. This study evaluated the effects of human atrial natriuretic peptide on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer.. A prospective, randomized study was conducted with 40 patients who had preoperative elevated B-type natriuretic peptide (≥ 30 pg/mL) and underwent a scheduled pulmonary resection for lung cancer. Results were compared between patients who received low-dose human atrial natriuretic peptide and those who received a placebo. The primary end point was the incidence of postoperative atrial fibrillation during the first 4 days after surgery.. The incidence of postoperative atrial fibrillation was significantly lower in the human atrial natriuretic peptide group than in the placebo group (10% vs 60%; P < .001). Patients in the human atrial natriuretic peptide group also showed significantly lower white blood cell counts and C-reactive protein levels after surgery.. Continuous infusion of low-dose human atrial natriuretic peptide during lung cancer surgery had a prophylactic effect against postoperative atrial fibrillation after pulmonary resection in patients with preoperative elevation of B-type natriuretic peptide levels. A larger sample size is needed to establish the safety and efficacy of this intervention.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Chi-Square Distribution; Double-Blind Method; Female; Hemodynamics; Humans; Infusions, Parenteral; Japan; Leukocyte Count; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Placebos; Pneumonectomy; Time Factors; Treatment Outcome; Up-Regulation

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

Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

Topics: Animals; Atrial Natriuretic Factor; Cell Adhesion; Cell Line, Tumor; Disease-Free Survival; Endothelial Cells; Green Fluorescent Proteins; Humans; Inflammation; Kaplan-Meier Estimate; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Retrospective Studies

Lung cancer patients with chronic obstructive pulmonary disease are at an increased risk of respiratory and cardiovascular complications after pulmonary resection. The objective of the present study was to evaluate the clinical effects of low-dose human atrial natriuretic peptide (hANP) on postoperative cardiopulmonary complications in untreated chronic obstructive pulmonary disease patients undergoing lung cancer surgery.. Of 824 patients who underwent an elective pulmonary resection procedure for lung cancer in two specialized thoracic centres between 2008 and 2011, 202 consecutive patients who had airflow limitation before surgery were included in this retrospective study. The results were compared between patients who did and those who did not receive hANP during the perioperative period. The primary endpoint was the incidence of postoperative cardiopulmonary complications. Postoperative haemodynamics, white blood cell (WBC) counts and C-reactive protein (CRP) levels were also examined. Furthermore, propensity score matching analysis was used to reduce treatment selection bias from patient characteristics.. The incidence of postoperative cardiopulmonary complications was significantly lower in the hANP group than in the control group (14 vs 36%, P < 0.01). The propensity score matching analysis confirmed the significantly decreased frequency of postoperative cardiopulmonary complications in the hANP group. Patients in the hANP group showed significantly lower WBC counts and serum CRP levels postoperatively.. Treatment with hANP during the perioperative period had a prophylactic effect against postoperative cardiopulmonary complications in chronic obstructive pulmonary disease patients undergoing lung cancer surgery.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; C-Reactive Protein; Cardiotonic Agents; Female; Heart Rate; Humans; Leukocyte Count; Lung Neoplasms; Male; Middle Aged; Perioperative Care; Postoperative Complications; Propensity Score; Pulmonary Disease, Chronic Obstructive

The objective of the present study was to evaluate the clinical effects of human atrial natriuretic peptide (hANP) on post-operative cardiopulmonary complications in elderly patients undergoing pulmonary resection for lung cancer.. A retrospective study involving 44 consecutive patients aged ≥75 years who had elevated pre-operative B-type natriuretic peptide levels (≥30 pg/ml) and underwent a scheduled pulmonary resection for lung cancer in two specialized thoracic centres between April 2008 and March 2010. Results were compared between the patients who did and did not receive hANP during the perioperative period. The primary endpoint was the incidence of post-operative cardiopulmonary complications. Post-operative haemodynamics, white blood cell (WBC) counts and C-reactive protein (CRP) levels were also examined.. The incidence of post-operative cardiopulmonary complications was significantly lower in the hANP group than that in the control group (26 vs. 86%, P < 0.0001). Patients in the hANP group showed significantly lower WBC counts and serum CRP levels post-operatively.. Continuous infusion of low-dose hANP during lung cancer surgery had a prophylactic effect on post-operative cardiopulmonary complications in elderly lung cancer patients. (. JPRN-UMIN000003631).

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Intravenous; Leukocyte Count; Lung Diseases; Lung Neoplasms; Male; Natriuretic Peptide, Brain; Perioperative Care; Postoperative Complications; Retrospective Studies; Treatment Outcome

Four cardiac peptide hormones, namely vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP) have anticancer effects.. The effects of these four cardiac hormones on human c-Jun-N-terminal kinase 2 (JNK2) were examined in human small cell lung cancer and human prostate cancer cells.. Vessel dilator, LANP, kaliuretic peptide and ANP maximally reduced expression of JNK2 by 89%, 56%, 45%, and 28%, respectively (each at p<0.0001) in human small cell lung cancer cells. In human prostate adenocarcinoma cells, JNK2 was maximally decreased 76%, 56%, 45%, (each at p<0.0001), and 28% (p<0.01) secondary to vessel dilator, LANP, kaliuretic peptide and ANP, respectively.. These results indicate that four cardiac hormones are significant inhibitors (by up to 89%) of JNK2 in human small cell lung cancer cells and up to 76% in human prostate adenocarcinoma cells as part of their anticancer mechanism(s) of action.

Topics: Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Humans; Lung Neoplasms; Mitogen-Activated Protein Kinase 9

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

To evaluate the usefulness of atrial natriuretic peptide (ANP) and brain B-type natriuretic peptide (BNP) for predicting postoperative atrial fibrillation (AF), we determined the changes in perioperative ANP and BNP levels in patients undergoing pulmonary resection for lung cancer.. This prospective observational study was conducted during the 10-month period from July 2007 to April 2008. Eighty patients with lung cancer underwent lobectomy, segmentectomy or wedge resection. Preoperative evaluations included spirometry and examinations of plasma ANP and BNP-levels, which were also determined on postoperative days 1, 3 and 7.. Postoperative AF was identified in 22 (28%) of the patients, and those had significantly higher preoperative ANP and BNP levels as compared with patients without AF. During the postoperative course, patients with postoperative AF also had significantly higher ANP and BNP-levels. The area under the receiver-operating characteristic curve for BNP to predict postoperative AF following pulmonary resection for lung cancer was 0.90 (95% confidence interval (CI), 0.82-0.98; p<0.001). A BNP value of 30pgml(-1) had a sensitivity of 77% and a specificity of 93% for predicting postoperative AF following pulmonary resection for lung cancer.. Preoperative BNP level seems to be an appropriate predictor of AF after pulmonary resection.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Female; Forced Expiratory Volume; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Pneumonectomy; Predictive Value of Tests; Prognosis; Prospective Studies; Vital Capacity

Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, long acting natriuretic peptide and kaliuretic peptide, have anticancer effects in vitro.. These cardiac hormones were infused subcutaneously for 28 days with weekly fresh hormones at 0.3 nM kg(-1) body weight in athymic mice bearing human squamous cell carcinomas.. Vessel dilator, atrial natriuretic peptide and kaliuretic peptide each eliminated one in six (17%) of the human squamous cell lung carcinomas. Long-acting natriuretic peptide, although it did not eliminate any of the human squamous cell lung carcinomas did decrease the volume of one carcinoma to only 2% (P < 0.0001) of the untreated carcinomas. The squamous cell lung carcinomas that were not eliminated, with the exception of the one LANP-treated tumour that decreased to only 2% of the volume of the untreated cancers, grew rapidly but their growth velocity compared to controls decreased by 76%, 40%, 38% and 25% in the vessel dilator, atrial natriuretic peptide, kaliuretic peptide and long-acting natriuretic peptide groups respectively (P < 0.05).. Three of four cardiac hormones synthesized by the atrial natriuretic peptide gene can eliminate human squamous cell lung carcinomas in athymic mice when treated subcutaneously for 4 weeks. The 4th cardiac hormone, i.e. long-acting natriuretic peptide, decreased the volume of one squamous cell lung carcinoma to 2% of that of untreated animals, suggesting that it, too, has beneficial effects on squamous cell lung cancers.

Topics: Animals; Antineoplastic Agents; Atrial Natriuretic Factor; Carcinoma, Squamous Cell; Cell Line, Tumor; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Peptide Fragments; Tumor Cells, Cultured

Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, long acting natriuretic peptide and kaliuretic peptide, and the kidney hormone urodilatin have anticancer effects in vitro.. These cardiac hormones and urodilatin were infused subcutaneously for 28 days with weekly fresh hormones since they lose biological effects at body temperature for more than a week at 0.3 nm kg(-1) body weight in athymic mice bearing human small-cell lung carcinomas.. Long acting natriuretic peptide, vessel dilator, kaliuretic peptide, atrial natriuretic peptide and urodilatin eliminated 86%, 71%, 57%, 43% (P < 0.001 for the cardiac hormones) and 25% (P < 0.05; urodilatin) of the human small-cell lung carcinomas. The treated small-cell lung carcinomas that were not cured grew rapidly, similar to the untreated controls, whose volume was 7 fold larger in 1 week, 18-fold increased in 2 weeks, 39-fold increased in 3 weeks, 63-fold increased in 1 month and 97-fold increased in volume in 6 weeks. One vessel dilator treated small-cell lung carcinoma animal developed a large tumour (8428 mm3 volume) on treatment and this tumour was eliminated with utilizing atrial natriuretic peptide and then long acting natriuretic peptide sequentially.. Four cardiac hormones eliminate up to 86% of human small-cell lung carcinomas in athymic mice. Urodilatin can also eliminate small-cell lung carcinomas but at a lower cure rate of 25%. Unresponsive lesions can be eliminated by utilizing different hormones synthesized by the atrial natriuretic peptide gene in a sequential manner.

Topics: Animals; Antineoplastic Agents; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Peptide Fragments; Protein Precursors; Receptors, Atrial Natriuretic Factor

Postoperative atrial fibrillation (AF) is a complication of thoracic surgery for lung cancer, with a reported incidence that can run as high as 42%. Recently, it has been observed retrospectively that B-type natriuretic peptide predicts AF after cardiac surgery. We performed a prospective study to evaluate the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a marker for risk stratification of postoperative AF in patients undergoing thoracic surgery for lung cancer.. We measured NT-proBNP levels in 400 patients (mean age, 62+/-10 years; 271 men) 24 hours before and 1 hour after surgery. The primary end point of the study was the incidence of postoperative AF. Overall, postoperative AF occurred in 72 patients (18%). Eighty-eight patients (22%) showed an elevated perioperative NT-proBNP value. When patients with either preoperatively or postoperatively elevated NT-proBNP were pooled, a greater incidence of AF was observed compared with patients with normal values (64% versus 5%; P<0.001). At multivariable analysis, adjusted for age, gender, major comorbidities, echocardiography parameters, pneumonectomy, and medications, both preoperative and postoperative NT-proBNP values were independent predictors of AF (relative risk, 27.9; 95% CI, 13.2 to 58.9; P<0.001 for preoperative NT-proBNP elevation; relative risk, 20.1; 95% CI, 5.8 to 69.4; P<0.001 for postoperative NT-proBNP elevation).. Elevation of perioperative NT-proBNP is a strong independent predictor of postoperative AF in patients undergoing thoracic surgery for lung cancer. This finding should facilitate studies of therapies to reduce AF in selected high-risk patients.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Incidence; Intraoperative Period; Lung Neoplasms; Male; Middle Aged; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Protein Precursors; Risk Factors; Sensitivity and Specificity; Thoracic Surgical Procedures

It is well documented in literature that a majority of small-cell lung cancers are associated with paraneoplastic phenomena. We report the case of a 63-year-old man diagnosed with small-cell lung carcinoma, in whom a severe hyponatremia and renal sodium loss with inappropriate antidiuresis were also found during a routine laboratory testing. Syndrome of inappropriate antidiuretic hormone secretion was first suspected in this patient, but another complex pathogenetic mechanism involving atrial natriuretic peptides could be associated, potentiating the deflation of the plasma sodium level. In our patient, the plasma-atrial natriuretic peptide base level, determined with a sensitive radioimmunoassay, was above the normal range (183 pg/mL; normal range, 50 pg/mL, +/- 10 pg/mL), and the antidiuretic hormone plasma level had an oscillatory pattern, varying between 5.5 pg/mL and 7 pg/mL (normal range, 0-4.7 pg/mL). We discuss the pathogenesis and clinical aspects of this association and the therapeutic options for these types of patients.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Middle Aged; Osmolar Concentration; Paraneoplastic Syndromes; Radiography; Radioimmunoassay; Sodium; Water-Electrolyte Imbalance

Within 24 h four peptide hormones, i.e. vessel dilator, long acting natriuretic peptide, kaliuretic peptide, and atrial natriuretic peptide and their intracellular mediator cyclic GMP decreased the number of human squamous lung cancer cells 51, 22, 25, 21, and 30%, respectively. There was not any proliferation in the 3 days following this decrease in cell number. Vessel dilator decreased DNA synthesis 85% in the squamous lung cancer cells. Thus, vessel dilator significantly decreased the number of human squamous lung cancer cells and their DNA synthesis, mediated in part by cyclic GMP, more than other peptide hormones.

Topics: Atrial Natriuretic Factor; Carcinoma, Squamous Cell; Cell Proliferation; Cyclic GMP; DNA Replication; DNA, Neoplasm; Humans; Lung Neoplasms; Peptide Fragments; Protein Precursors; Tumor Cells, Cultured

Four peptide hormones of a family of six hormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-natriuretic peptide (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number of adenocarcinoma cells in culture. The present investigation was designed to determine whether these peptide hormones' effects are specific to adenocarcinomas or whether they might decrease the number of cancer cells of a different type of cancer, i.e. small-cell lung cancer.. These six hormones were evaluated for their ability to decrease the number and/or proliferation of human small-cell lung cancer cells in culture for 24, 48, 72, and 96 h.. Within 24 h, vessel dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic GMP, each at 1 microM, decreased the number of small-cell lung cancer cells by 63% (P < 0.001), 21% (P < 0.05), 30% (P < 0.05), 39% (P < 0.05), and 31% (P < 0.05), respectively. There was no proliferation in the 3 days following this decrease in cell number. These same hormones decreased DNA synthesis 68% to 82% (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of small-cell lung cancer cells or inhibit their DNA synthesis at 1 microM or 10 microM concentrations. Dose-response curves revealed that at 100 microM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease. Western blots revealed that the natriuretic peptide receptors A- and C- were present in these cancer cells.. Five peptide hormones significantly decrease the number of human small-cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.

Topics: Adenocarcinoma; Atrial Natriuretic Factor; Blotting, Western; Carcinoma, Small Cell; Cell Proliferation; Humans; Lung Neoplasms; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Protein Precursors

From August 1997 to December 2002, 14 consecutive patients with superior vena cava syndrome with the self-expanding endovascular prosthesis. Diagnoses were adenocarcinoma in 6, small cell carcinoma in 4, squamous cell carcinoma in 1, metastatic lung cancer in 2, and invasive thymoma in 1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured on their admission and perioperative period. Expecting only 1 patient complete symptomatically relieved within 3 days of stent implantation. Superior vena cava pressure or radial pressure of the stent was sufficient to relieve obstruction. Preoperative ANP level were normal, BNP level were increased. Postoperatively both ANP level and BNP level were slightly increased under intravenous dopamine hydrochloride. Implantation of the self-expanding stent endovascular prosthesis for superior vena cava syndrome provides rapid symptomatic relief and improves the patient's quality of life.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prostheses and Implants; Quality of Life; Stents; Superior Vena Cava Syndrome

Corin is a recently discovered pro-atrial natriuretic peptide (ANP) convertase that is abundantly expressed in the heart. ANP is a cardiac hormone but can be secreted ectopically by certain cancers including small cell lung cancer (SCLC). In this study, we examined the role of corin in ANP production by SCLC cells. Reverse transcription-PCR detected corin mRNA expression in all nine SCLC cell lines examined and ANP mRNA expression in seven of the nine cell lines. In contrast, arginine vasopressin mRNA was detected in only five of the nine SCLC cell lines studied. Corin-expressing SCLC cells were capable of converting recombinant human pro-ANP to biologically active ANP, as determined by Western analysis and a cyclic GMP assay. Transfection of small interfering RNA duplexes directed against the corin gene completely blocked the processing of pro-ANP in the SCLC cells. Our results show that corin functions as a pro-ANP convertase in SCLC cells. We also suggest that the expression of corin may contribute to the pathogenesis of the syndrome of inappropriate secretion of antidiuretic hormone associated with certain cancers.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Cell Line, Tumor; Humans; Lung Neoplasms; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Serine Endopeptidases; Transfection

Little is known about alterations in the levels and influence of natriuretic peptide (NP) on cardiopulmonary function after pulmonary resection for lung cancer. This study was designed to investigate the patterns and activity of NP after pulmonary resection.. We investigated changes in plasma A-type (atrial) NP and B-type (brain) NP (BNP) using radioimmunoassay, in lung cancer patients before and after lobectomy (n = 15) or pneumonectomy (n = 10). Patient characteristics, respiratory function, operative time, blood loss, intraoperative fluid administration, and intraoperative urine output in both groups were also compared. Pulmonary hemodynamic variables were monitored continuously.. Plasma concentrations of A-type NP and BNP did not differ between the two groups preoperatively. However, the group undergoing pneumonectomy exhibited higher concentrations of A-type NP and BNP than the group undergoing lobectomy on postoperative days 3 and 7. Alterations in A-type NP and BNP after pulmonary resection therefore differed according to the volume of lung tissue resected. Both mean pulmonary artery pressure and total pulmonary vascular resistance increased significantly in the pneumonectomy group. The total pulmonary vascular resistance on postoperative day 3 correlated with the plasma BNP concentration in the pneumonectomy group.. A-type NP and BNP effectively compensate for the right ventricular dysfunction noted after pulmonary resection, and this is more evident after pneumonectomy than after lobectomy. Changes in ventricular activity associated with changes in plasma BNP and total pulmonary vascular resistance are indicative of cardiopulmonary adjustments after pneumonectomy.

Topics: Aged; Atrial Natriuretic Factor; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Pneumonectomy; Postoperative Complications; Pulmonary Wedge Pressure; Radioimmunoassay; Vascular Resistance

Tumors and tumor cell lines from two patients with small cell lung carcinoma (SCLC) (one with and one without hyponatremia) were studied. Ectopic production and prohormone processing of atrial natriuretic peptide (ANP) were investigated to determine if a biologically active peptide was produced in a tumor cell line from a patient with hyponatremia and no evidence of arginine vasopressin (AVP) production.. Ribonuclease (RNase) protection assays were performed on mRNA isolated from tumors and tumor cell lines established from two SCLC patients, one with and one without hyponatremia. Cellular extracts and conditioned media were studied using reversed-phase high performance liquid chromatography (HPLC) to determine the immunoreactive form of ANP. Tumor cell line sonicates were studied for subcellular localization of enzymatic activity that cleaved pro-ANP peptide substrates.. RNase protection assays showed a 200-base pair protected fragment in the mRNA isolated from the tumor and tumor cell line from the patient with hyponatremia (Patient 4). HPLC characterization of the cellular extract and conditioned medium from the tumor and tumor cell line from Patient 4 demonstrated ANP immunoreactivity in the same fraction as ANP- (S99-Y126). The tumor cell line extract that localizes to a subcellular fraction enriched for lysosomes and secretory organelles contains a 60-kilodalton molecular weight protein with enzyme activity that hydrolyzes synthetic pro-ANP substrates and catalyzes the formation of ANP-(S99-Y126).. A tumor cell line from a patient with hyponatremia was able ectopically to produce, process, and secrete ANP in the same immunoreactive form as the biologically active molecule. Preliminary studies show that tumor cell line NCI-H1284 contains an enzyme that can cleave precursors at the same amino acid sequences needed to produce ANP-(S99-Y126) from pro-ANP.

Topics: Atrial Natriuretic Factor; Carcinoma, Small Cell; Chromatography, High Pressure Liquid; Humans; Hyponatremia; Lung Neoplasms; Male; Neoplasm Proteins; RNA, Messenger; Tumor Cells, Cultured

This study was undertaken to define the impact of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) on sodium homeostasis in patients with lung cancer. Patients had their serum and urine electrolytes and osmolality determined before and after a saline infusion of 500 ml. The plasma hormones, AVP, ANP, plasma renin activity (PRA), angiotensin II, and aldosterone were determined by radioimmunoassay every 15 min before, during and after the saline infusion. Fifty patients, 31 with small cell lung cancer and 19 with non-small cell lung cancer participated in this trial. All 11 patients (10 patients with small cell lung cancer and one patient with non-small cell lung cancer) who presented with hyponatremia had inappropriately elevated levels of AVP. Elevated plasma AVP levels were highly correlated with the presence of hyponatremia (p < 0.00001). Initial plasma ANP levels were not associated with hyponatremia (p = 0.73). Urinary sodium concentration increased during the saline infusion proportional to the initial plasma level of ANP (p = 0.0045). AVP appears to be elevated in nearly all patients with hyponatremia of malignancy. ANP plasma levels in patients with lung cancer are associated with the ability to excrete a sodium load but do not appear to downregulate renin, angiotensin II, and aldosterone production.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Homeostasis; Hormones, Ectopic; Humans; Hyponatremia; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Renin; Sodium; Tumor Cells, Cultured

Hyponatremia in patients with small cell lung cancer (SCLC) is a common clinical problem usually attributed to tumor secretion of arginine vasopressin (AVP). It recently was shown that some SCLC cell lines produce atrial natriuretic peptide (ANP). The purpose of this investigation was to determine the frequency and clinical consequences of secretion of ANP by SCLC and the relative contribution of ANP and AVP to the hyponatremia associated with this disease.. Levels of ANP and AVP were measured in 23 SCLC cell lines and 23 other human tumor cell lines. Also, ANP and AVP levels were determined in plasma samples from 69 patients with active small cell carcinomas.. Of the 23 SCLC lines, 16 (70%) had elevated ANP levels. Only two (8.7%) had elevated AVP levels, and these two also had elevated ANP levels. One of the ANP-producing cell lines was derived from a hyponatremic patient with no other apparent explanation for a low sodium level. However, the four cell lines with the highest levels of ANP were derived from patients who were not hyponatremic. Two other human tumor lines also produced ANP. Of the 69 patients with SCLC, 21 (30.4%) had elevated ANP levels, whereas 4 (6%) had elevated AVP levels. Fifteen of these patients were hyponatremic during their clinical course (21.7%). Of the eight patients who were hyponatremic when samples were collected, two had elevated ANP levels, and only one had elevated AVP levels. Six patients (8.7%) had symptoms of postural hypotension, possibly attributable in some cases of tumor secretion of ANP.. The majority of SCLC lines produce ANP, and a minority produce AVP. Secretion of ANP may result in hyponatremia and/or postural hypotension. However, secretion of either or both of these peptides does not account for all cases of hyponatremia in patients with SCLC and does not necessarily cause clinical manifestations.

Topics: Adenocarcinoma; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Humans; Hyponatremia; Hypotension, Orthostatic; Lung Neoplasms; Male; Sodium; Tumor Cells, Cultured

To determine whether inappropriately secreted vasodilatory peptides have a role in the pathogenesis of orthostatic (postural) hypotension, a recognised paraneoplastic effect of bronchial malignancies usually attributed to immune mediated destruction of autonomic ganglia.. Serum concentrations of three vasodilatory peptides, atrial natriuretic peptide (ANP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP), were measured in 111 patients with bronchial carcinoma and 35 controls prospectively screened for orthostatic hypotension (> 20 mmHg drop in systolic blood pressure on repeated occasions on standing from the supine position) and in whom other causes of this condition were excluded.. Twenty two (20%) patients with carcinoma and two (6%) controls had orthostatic hypotension according to the criteria used. Serum concentrations of ANP, VIP and CGRP were elevated above normal in, respectively, 25 (23%), 10 (9%) and eight (7%) patients with carcinoma and in six (18%), zero and three (9%) controls. There was no correlation between orthostatic hypotension and concentrations of any of the vasodilatory peptides.. Elevated serum concentrations of ANP and CGRP were no more frequent in subjects with bronchial carcinoma than in controls and could not be attributed to the tumour, although there was a possible association for VIP. Orthostatic hypotension was more common in patients with carcinoma, but there was no evidence that the peptides measured played a role in its pathogenesis.

Topics: Aged; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Case-Control Studies; Humans; Hypotension, Orthostatic; Lung Neoplasms; Middle Aged; Paraneoplastic Syndromes; Prospective Studies; Vasoactive Intestinal Peptide

To test the hypothesis that neural mechanisms evoked by unilateral pulmonary artery occlusion (UPAO) affect the release of atrial natriuretic peptides (ANP) from the heart, hemodynamics and levels of plasma ANP and cyclic guanosine monophosphate (c-GMP) were studied in 11 patients with lung cancer. The UPAO induced a significant rise in heart rate by 5.3 percent, increased mean pulmonary artery pressure by 31 percent without affecting right atrial pressure, and decreased plasma ANP levels in the coronary sinus by 17.4 percent (p < 0.05) from 202.5 +/- 27.1 pg/ml to 167.2 +/- 27.4 pg/ml. Atropine sulfate (0.04 mg/kg) injection increased the heart rate by 38.2 percent (p < 0.01), reduced the stroke volume index by 25.1 percent, decreased coronary sinus ANP levels from 198.5 +/- 16.4 pg/ml to 124.8 +/- 19.6 pg/ml (p < 0.01), and decreased coronary sinus plasma c-GMP levels from 4.6 +/- 0.5 pmol/ml to 3.1 +/- 0.4 pmol/ml (p < 0.05). After atropine pretreatment, UPAO induced a significant (p < 0.05) increase of 34.8 percent in the coronary sinus ANP level. Thus, it is concluded that in UPAO, the secretion of ANP from the heart is modulated partly by the autonomic nervous system.

Topics: Adenocarcinoma; Aged; Atrial Natriuretic Factor; Atropine; Carcinoma, Squamous Cell; Catheterization, Peripheral; Cyclic GMP; Female; Heart; Hemodynamics; Humans; Lung Neoplasms; Male; Middle Aged; Pulmonary Artery; Time Factors

Peptide hormone synthesis in neuroendocrine tumors is a well-recognized phenomenon. However, production in neuroendocrine tumors of atrial natriuretic polypeptide (ANP), a newly discovered peptide hormone from the heart, has not been studied extensively.. The presence of immunoreactive human ANP (IR-hANP) in neuroendocrine tumors was determined using a specific human ANP radioimmunoassay. Neuroendocrine tumors examined included 9 small cell carcinomas of the uterus, 28 small cell carcinomas of the lung, 20 carcinoid tumors, 54 pancreatic endocrine tumors, 17 neuroblastic tumors, 14 pheochromocytomas, and 14 medullary carcinomas of the thyroid. Twenty atrial tissues also were examined as the control. Molecular size of IR-hANP in the extracts of atrial and tumor tissues was determined by gel chromatography.. IR-hANP was detected in the extracts of small cell carcinoma of the uterus, small cell carcinoma of the lung, and carcinoid tumor, with concentrations ranging from 3.1 to 210 ng/g wet weight tissue. No IR-hANP was detected in the extracts of pancreatic endocrine tumor, neuroblastic tumor, pheochromocytoma, and medullary carcinoma of the thyroid. The frequency of production of IR-hANP in neuroendocrine tumors was highest in small cell carcinoma of the uterus (44%), followed by small cell carcinoma of the lung (18%) and carcinoid tumor (15%). IR-hANP present in the extracts of small cell carcinomas of the uterus had molecular size heterogeneity, with three fragments in addition to alpha-, beta- and gamma-human ANP.. These results indicate that IR-hANP is produced by neuroendocrine tumors and that the molecular size of IR-hANP in tumor tissues is different from that in atrial tissues.

Topics: Atrial Natriuretic Factor; Carcinoid Tumor; Carcinoma, Small Cell; Female; Humans; Lung Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Pheochromocytoma; Radioimmunoassay; Thyroid Neoplasms; Uterine Neoplasms

Topics: Aged; Atrial Natriuretic Factor; Humans; Lung Neoplasms; Male; Middle Aged; Pneumonectomy; Postoperative Period; Prognosis; Radioimmunoassay

Patients with lung cancer (n = 263) were studied to determine the relationship among ectopic production of atrial natriuretic factors (ANF) and arginine vasopressin (AVP), serum sodium, and patient outcome. Of 133, 21 (16%) patients with small cell lung cancer (SCLC) had hyponatremia (serum sodium, < 130 mmol/liter), compared to none of 130 (0%) patients with non-small cell lung cancer (P < 0.0001). Patients with extensive-stage SCLC and hyponatremia had shorter survival than patients with extensive stage SCLC and normal serum sodium values (P = 0.012). Of the 11 hyponatremic patients with SCLC and tumor cell lines available for study, 9 produced ANF mRNA, 7 of 11 produced AVP mRNA, and 5 of 11 produced both ANF mRNA and AVP mRNA. All 11 cell lines produced either ANF mRNA and ANF peptide or AVP mRNA and AVP peptide, or both. The quantity of AVP peptide in the tumor cell lines was more closely associated with hyponatremia in the patients (P = 0.0026, r2 = 0.28) than was the production of ANF peptide (P = 0.066, r2 = 0.12), although neither association was strong. All tumor cell lines studied from SCLC patients with hyponatremia produce ANF and/or AVP mRNA and peptides.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Prognosis; Radioimmunoassay; Ribonucleases; RNA, Messenger; Sodium; Tumor Cells, Cultured

We describe a patient who presented with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 2 months before clinical evidence of bronchogenic malignancy. Because of the potential for the ectopic production of atrial natriuretic peptide (ANP) to mimic SIADH, both hormones were measured in this hyponatremic patient to seek a possible marker of tumor activity. A hypertonic saline infusion at presentation revealed excessive osmotically decoupled secretion of arginine vasopressin but a normal ANP response.

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Saline Solution, Hypertonic

Small cell lung cancer cell (SCLC) lines, NCI-H82, NCI-H660, and NCI-H1284, and HeLa cells were analyzed for the presence of atrial natriuretic peptide (ANP) receptors. In these SCLC cell lines and HeLa cells, ANP A receptor mRNA was identified by Southern blot analyses of polymerase chain reaction products and RNase protection assays using poly(A)(+)-selected RNA. Saturable binding assays revealed that HeLa cells had 2000 to 5000 high affinity atrial natriuretic peptide receptors per cell with a dissociation constant of 140 pM. In the SCLC cell lines, the binding was saturable but too low to accurately estimate the number of binding sites. After addition of human ANP, radioimmunoassays revealed accumulation of cyclic GMP in SCLC cells as well as HeLa cells in a dose-dependent fashion. The half-maximal stimulation concentration of cyclic GMP accumulation in HeLa and these SCLC cell lines was approximately 2 nM. Tetrazolyl blue assays and tritiated thymidine incorporation did not show any remarkable growth inhibition or growth stimulation of SCLC cell lines after addition of human ANP up to 3.3 microM, more than 1000-fold greater than the half-maximal stimulation concentration of cyclic GMP accumulation. Our results indicate that human SCLC cells express functional ANP receptors but ANP addition produced no detectable change in their growth pattern.

Topics: Atrial Natriuretic Factor; Base Sequence; Blotting, Southern; Carcinoma, Small Cell; Cell Division; Cyclic GMP; HeLa Cells; Humans; Iodine Radioisotopes; Lung Neoplasms; Molecular Sequence Data; Polymerase Chain Reaction; Radioimmunoassay; Receptors, Atrial Natriuretic Factor; Ribonucleases; RNA, Messenger; Stimulation, Chemical; Tetrazolium Salts; Thiazoles; Thymidine; Tritium; Tumor Cells, Cultured

One autopsy case with small cell lung cancer and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is reported. Both plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) levels were high, and the presence of significantly high levels of ANP and AVP in tumor tissue was confirmed by gel chromatography and radioimmunoassay techniques. To the best of the authors' knowledge, this is the first case in which ectopic ANP production and its secretion into blood (leading to SIADH) were proved.

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Electrolytes; Female; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Paraneoplastic Endocrine Syndromes

In the present study, we investigated whether release of hANP increases during mild and long-term volume loading. Eight lung cancer patients in good performance state (five men and three women, 35 to 68 years), who needed to have pre-hydration for cancer chemotherapy with cisplatin, were infused with about seven liters of isotonic saline over 48 hours through Swan-Ganz catheter placed in the pulmonary artery. The mean infusion rate was 0.042 ml/min.kg body weight. During the infusion, change in plasma volume (delta PV) increased by 5.8 + 3.3 (mean +/- SE) %. Right atrial pressure (RAP) did not change significantly, and pulmonary artery wedge pressure (PAWP) increased from 4.3 +/- 1.0 to 5.8 +/- 0.7 mmHg. Plasma hANP was significantly elevated from 50.6 +/- 0.7 to 105.1 +/- 19.3 pg/ml by the second day of the infusion with a suppression of plasma renin activity (PRA) and aldosterone, though plasma ADH did not change. The infusion rate at 20:00 on the first day was the same as that on the second day. Further increase in plasma hANP was shown at 20:00 on the second day compared with the level at the same time on the first day, though RAP, PAWP and delta PV did not change. These results indicate that mild and chronic volume loading increases plasma hANP, and suggest that the prolongation of volume expansion plays an important role in the releasing of hANP in humans.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Hemodynamics; Humans; Infusions, Intra-Arterial; Isotonic Solutions; Lung Neoplasms; Male; Middle Aged; Pulmonary Artery; Sodium Chloride

Increased capillary permeability and severe hypotension represent the two major cardiovascular complications of IL-2 immunotherapy. The mechanisms responsible for IL-2 cardiovascular toxicity are still obscure. Since increased vascular permeability and vasodilatation may be also induced by the cardiac hormone atrial natriuretic peptide (ANP), we have evaluated ANP concentrations in relation to mean arterial pressure in one patient with metastatic renal carcinoma, treated with a 24-h intravenous infusion of IL-2 at a dose of 3 x 10(6) Cetus U/m2/day for 5 days. The results showed that episodes of important hypotension were associated with abnormally high plasma levels of ANP. Owing to its vasodilator activity, exaggerated ANP secretion, perhaps due to an inappropriate cardiac endocrine function in response to hemodynamic changes induced by IL-2, may play a role in hypotension, which occurs during IL-2 immunotherapy for cancer.

Topics: Atrial Natriuretic Factor; Capillary Permeability; Drug Administration Schedule; Female; Humans; Hypotension; Interleukin-2; Kidney Neoplasms; Lung Neoplasms; Middle Aged; Vaginal Neoplasms

Hyponatremia in patients with small cell lung cancer can be caused by tumor production of arginine vasopressin (AVP) and result in the syndrome of inappropriate antidiuretic hormone. In evaluating the expression of AVP mRNA from tumor and tumor cell line specimens from five patients with small cell lung cancer and hyponatremia (presumed to have the syndrome of inappropriate antidiuretic hormone), we found that the tumors and tumor cell lines from two of these five patients expressed AVP mRNA. The RNA samples from the three patients with undetectable AVP mRNA expressed abundant atrial natriuretic factor (ANF) mRNA. Analysis of specimens from three patients with small cell lung cancer and normal serum sodium levels revealed no detectable AVP mRNA expression, and samples from only one of these three patients' specimens expressed detectable ANF mRNA. The AVP and ANF peptide levels in lysate preparations of the tumor cell lines from four of these patients were tested by radioimmunoassay and confirmed the gene expression data. These studies demonstrate ectopic production of ANF mRNA in small cell lung cancer specimens from patients with this cancer and the syndrome of inappropriate antidiuretic hormone. These findings will be of particular interest if future studies demonstrate that ectopic ANF production can cause sodium abnormalities in patients with small cell lung cancer.

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Blotting, Northern; Carcinoma, Small Cell; Gene Expression Regulation, Neoplastic; Hormones, Ectopic; Humans; Hyponatremia; Lung Neoplasms; Middle Aged; Radioimmunoassay; RNA, Messenger; RNA, Neoplasm; Single-Strand Specific DNA and RNA Endonucleases; Tumor Cells, Cultured

The present studies were undertaken to assess the effects of atrial natriuretic factor (ANF) on erythropoietin (Ep) secretion in Ep-producing renal carcinoma (RC) cells using a sensitive radioimmunoassay for Ep. Human ANF produced a significant dose-related increase in Ep secretion at concentrations of 10(-7) and 10(-6) M when compared with vehicle controls. ANF (greater than or equal to 10(-9) M) also significantly increased the intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration after 5-min incubation with the RC cells. Scatchard analysis of the human 125I-labeled ANF binding data indicated that the RC cells contain a single class of binding sites with a dissociation constant (Kd) of 93 +/- 1 pM and a binding capacity of 2,190 +/- 750 sites/cell. Incubation of the RC cells with 8-bromo-cGMP in concentrations of 10(-7)-10(-5) M also produced a significant dose-related enhancement of Ep secretion. These findings suggest that the increase in Ep secretion in response to ANF can be attributed, at least in part, to activation of guanylate cyclase, which is coupled to specific ANF receptors on the RC cell.

Topics: Atrial Natriuretic Factor; Carcinoma, Renal Cell; Cyclic GMP; Erythropoietin; Humans; Kidney Neoplasms; Kinetics; Lung Neoplasms; Tumor Cells, Cultured

Atrial natriuretic factor is a new peptide hormone synthesized in the heart which has potent natriuretic, diuretic, and vasodilatory properties. A 47-year-old man with squamous cell carcinoma of the lung resected 6 months previously presented with syncope secondary to hypotension and a low serum sodium. He was evaluated to determine if atrial natriuretic factor (ANF) might be the etiology of this clinical picture. His plasma concentration of atrial natriuretic factor was increased three-fold over that of 70 normotensive person. Further evaluation revealed metastatic lesions in the right and left cardiac atria with the mass on the left occluding 75% of the left atrial chamber. The mass effect in the atria increasing atrial stretch and atrial pressure one would expect was the main contributor to the increased ANF level. The contribution of direct tumor invasion into the atria and/or production of atrial natriuretic factor by the tumor itself to produce this elevated plasma level of atrial natriuretic factor could not be determined, but this markedly elevated level of atrial natriuretic factor does appear to be the etiology of this patient's clinical picture.

Topics: Atrial Natriuretic Factor; Biomarkers, Tumor; Carcinoma, Squamous Cell; Echocardiography; Heart Atria; Heart Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Radioimmunoassay

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Breast Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pericardial Effusion; Pericardium; Punctures; Suction; Time Factors

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Hormones, Ectopic; Humans; Lung Neoplasms; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Protein Precursors; Vasopressins

Specific radioimmunoassay and immunohistochemical method of alpha-human atrial natriuretic polypeptide (alpha-hANP) was established to diagnose one case of large cell lung carcinoma (clear cell carcinoma) proved by pathology. It was found that there was alpha-hANP-like immunoreactivity in the cancer cells at a concentration of 147.5 pg/mg protein. Chromatography analysis showed that alpha-hANP-like immunoreactive materials had multiple molecular forms. The significance of these phenomena remains to be further investigated.

Topics: Adenocarcinoma; Atrial Natriuretic Factor; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Peptide Fragments; Radioimmunoassay

A 62-year-old man with small cell carcinoma (oat cell type) of the lung who had hyponatremia and renal sodium loss with inappropriate antidiuresis is reported. Plasma levels of arginine vasopressin (AVP) were not elevated inappropriately. Plasma levels of atrial natriuretic peptide (ANP), however, were high, and increased after water loading and hypertonic saline infusion. The renin-aldosterone axis was normal, as were adrenal, thyroid, and renal functions. Water restriction to 500 to 700 ml/d resulted in a rise in serum sodium. Analysis of the tumor tissue failed to demonstrate the presence of AVP or ANP. The findings (1) suggest that hyponatremia and renal sodium loss with inappropriate antidiuresis observed in the patient is due to an antidiuretic substance distinct from AVP, and (2) point to the possibility that hypersecretion of ANP may play a role in the pathophysiology.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Middle Aged; Saline Solution, Hypertonic; Water