atrial-natriuretic-factor and Kidney-Neoplasms

Protein kinase-B (AKT) is a serine/threonine protein kinase that has a key role in cell proliferation and cancer cell invasiveness. Four cardiac peptide hormones, namely vessel dilator, atrial natriuretic peptide (ANP), kaliuretic peptide, and long-acting natriuretic peptide (LANP) have anticancer effects both in vitro and in vivo.. Four cardiac hormones were examined for their ability to inhibit AKT, measured with a solid-phase enzyme-linked immunosorbent assay (ELISA) in human colorectal, pancreatic, and renal cancer cells.. Vessel dilator, kaliuretic peptide, ANP, and LANP maximally reduced the concentration of AKT by 47%, 45%, 52%, and 46% in human colorectal cancer cells (p<0.0001), by 60%, 61%, 64%, and 59% in human pancreatic carcinoma cells (p<0.0001), and by 31%, 32%, 31%, and 31% in renal adenocarcinoma cells (p<0.001).. These four cardiac hormones are significant inhibitors of AKT in human cancer cells, as part of their anticancer mechanism(s) of action.

Topics: Adenocarcinoma; Antineoplastic Agents; Atrial Natriuretic Factor; Cell Line, Tumor; Colorectal Neoplasms; Humans; Kidney Neoplasms; Pancreatic Neoplasms; Peptide Fragments; Protein Precursors; Proto-Oncogene Proteins c-akt

β-Catenin causes malignant growth of colonic, pancreatic and renal cancer. Four cardiac hormones, namely atrial natriuretic peptide (ANP), vessel dilator, long-acting natriuretic peptide (LANP) and kaliuretic peptide eliminate up to 80% of human pancreatic carcinomas growing in mice.. Four cardiac hormones were evaluated for their ability to reduce the expression of human β-catenin, measured by enzyme-linked immunosorbent assay (ELISA) in human colorectal, pancreatic and renal cancer cells.. Vessel dilator, LANP, kaliuretic peptide, and ANP, over a concentration range of 100 pM to 10 μM, maximally reduced expression of β-catenin in human colorectal cancer cells by 78%, 71%, 69%, and 83%, respectively. Vessel dilator, LANP, kaliuretic peptide, and ANP reduced β-catenin expression in human pancreatic cancer cells by 76%, 66%, 72%, and 88%, and by 64%, 54%, 58% and 73%, in human renal cancer cells, respectively.. Part of the anticancer action of these four cardiac hormones is a potent inhibition of β-catenin.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Atrial Natriuretic Factor; beta Catenin; Cell Line, Tumor; Colonic Neoplasms; Colorectal Neoplasms; Humans; Kidney Neoplasms; Mice; Pancreatic Neoplasms; Peptide Fragments; Protein Precursors

We used human DNA microarray to explore the differential gene expression profiling of atrial natriuretic peptide (ANP)-stimulated renal tubular epithelial kidney cells (LLC-PK1) in order to understand the biological effect of ANP on renal kidney cell's response. Gene expression profiling revealed 807 differentially expressed genes, consisting of 483 up-regulated and 324 down-regulated genes. The bioinformatics tool was used to gain a better understanding of differentially expressed genes in porcine genome homologous with human genome and to search the gene ontology and category classification, such as cellular component, molecular function and biological process. Four up-regulated genes of ATP1B1, H3F3A, ITGB1 and RHO that were typically validated by real-time quantitative PCR (RT-qPCR) analysis serve important roles in the alleviation of renal hypertrophy as well as other related effects. Therefore, the human array can be used for gene expression analysis in pig kidney cells and we believe that our findings of differentially expressed genes served as genetic markers and biological functions can lead to a better understanding of ANP action on the renal protective system and may be used for further therapeutic application.

Topics: Atrial Natriuretic Factor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Kidney Tubules; LLC-PK1 Cells; Oligonucleotide Array Sequence Analysis

Mortality from renal-cell cancer remains a significant problem with an estimated 12,600 deaths in the United States in 2005 even with current treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide and kaliuretic peptide have significant anti-cancer effects in breast, pancreatic, prostate and colon adenocarcinomas.. These four peptide hormones plus brain natriuretic peptide (BNP), C-natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney by a different post-translational processing of the atrial natriuretic peptide prohormone, were evaluated for their anti-cancer effects in renal carcinomas.. Dose-response curves revealed a significant (P < 0.0001) decrease in human renal carcinoma cells with each 10-fold increase in concentration from 1 microm to 100 microm of five of these peptide hormones. There was an 81%, 74%, 66%, 70% and 70% elimination within 24 h in renal carcinoma cells secondary to vessel dilator, kaliuretic peptide, urodilatin, atrial natriuretic peptide and long-acting natriuretic peptide, respectively (P < 0.0001 for each), whereas BNP had no effect and CNP decreased renal cancer cell number by 10% (P = 0.04) at their 100 microm concentrations. Three days after treatment with these peptide hormones, the cancer cells began to proliferate again. The four cardiac hormones and urodilatin decreased DNA synthesis from 65-84% (P < 0.00001), whereas BNP and CNP decreased DNA synthesis 3% and 12% (both non-significant). Western blots revealed for the first time natriuretic peptide receptors (NPR)-A, -B and -C were present in the renal cancer cells.. These results indicate that urodilatin and the four cardiac hormones have potent anti-cancer effects by eliminating up to 81% of renal carcinoma cells within 24 h of treatment.

Topics: Aged; Antineoplastic Agents; Atrial Natriuretic Factor; Carcinoma, Renal Cell; Cell Proliferation; Humans; Kidney Neoplasms; Male; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Atrial Natriuretic Factor

Renin secretion in response to long-term exposure to isoprenaline, dibutyryl cyclic adenosine monophosphate (dbcAMP), forskolin and atrial natriuretic peptide (ANP) was measured in cultured human nephroblastoma cells.. Human nephroblastoma cells in culture were treated long-term (1-12 days) with isoprenaline, dbcAMP or forskolin, alone or in combination with ANP; renin release and cell growth were studied.. The increase in renin output caused by isoprenaline and dbcAMP could be accounted for by stimulation of cell growth. The effect of isoprenaline was blocked by propranolol. Forskolin stimulated renin secretion per cell. ANP increased extracellular cyclic guanosine monophosphate and suppressed basal renin output. Suppression of basal renin output was due to a reduced secretion rate per cell, without a change in cell growth. ANP suppressed isoprenaline-induced and dbcAMP-induced renin output by blocking increased cell growth, and forskolin-induced renin output by blocking renin secretion.. These results suggest that beta-receptor agonists and ANP interact within the kidney to control renin secretion, by helping to determine the number of renin-secreting cells.

Topics: Atrial Natriuretic Factor; Bucladesine; Colforsin; Humans; In Vitro Techniques; Isoproterenol; Kidney Neoplasms; Propranolol; Renin; Time Factors; Tumor Cells, Cultured; Wilms Tumor

Increasing evidence indicates that angiotensin II can be formed by juxtaglomerular cells (JGC) and cosecreted with renin. We investigated the existence of this local renin-angiotensin system in a human JGC tumor, using an in vitro superfusion. The JGC tumor was found concomitantly to release renin and angiotensin I and II. Sequential addition of atrial natriuretic peptide, dopamine, and a somatostatin analog in the superfusion did not affect renin or angiotensin I and II release. The data provide evidence that the human JGC tumor in vitro generates angiotensin II, and supports its possible role as a local in vivo regulator of kidney function.

Topics: Adult; Angiotensin I; Angiotensin II; Atrial Natriuretic Factor; Dopamine; Female; Humans; Juxtaglomerular Apparatus; Kidney Neoplasms; Microscopy, Electron; Octreotide; Perfusion; Renin

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

1. A 17 year old female presented with severe hypertension, hypokalaemia and elevated levels of plasma renin activity due to a renin-secreting tumour. 2. Renin was responsive to posture, low sodium diet, saline infusion and frusemide, but relatively unresponsive to raising or lowering circulating levels of angiotensin II. 3. Renal venous renin levels lateralized to the side of the tumour with good contralateral suppression when measured with control of posture and avoidance of prior stimulation, with and without angiotensin converting enzyme inhibition. 4. Levels of atrial natriuretic peptide were elevated and responsive to posture, saline infusion and angiotensin infusion. 5. The tumour was evident on computerized tomography, but not on intravenous pyelography or renal angiography. 6. Responsiveness of renin secretion to normal stimuli in reninoma may make diagnosis difficult, and renal vein sampling under controlled conditions is necessary.

Topics: Adolescent; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Blood Volume; Female; Humans; Kidney Neoplasms; Peptidyl-Dipeptidase A; Posture; Renal Veins; Renin

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

Specific binding sites for atrial natriuretic peptide (99-126) in different areas of normal human renal tissue were quantified by in vitro autoradiography. Our data represent the first characterization of ANP binding sites in different structures of the human kidney. Characterization of ANP binding revealed by Scatchard plot analysis a single class of high affinity binding sites in the glomeruli (Kd 0.53 +/- 0.11 nM; BMax 74.4 +/- 17.86 fmol/mg protein), the vasculature (Kd 0.18 +/- 0.014 nM; BMax 91.6 +/- 25.02 fmol/mg protein), and the medulla (Kd 0.34 +/- 0.13 nM; BMax 106.0 +/- 30.61 fmol/mg protein). These sites may play a key role in the actions of the cardiac hormone in human kidney and in the ameliorating effects of ANP in the recovery from acute renal failure.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Autoradiography; Carcinoma, Renal Cell; Female; Humans; Kidney; Kidney Neoplasms; Male; Middle Aged; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface