Cardiac hormones for the treatment of cancer.

Endocr Relat Cancer. 2013 Mar 26;

Authors: Vesely DL

Abstract
Four cardiac hormones namely, atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, reduce up to 97% of all cancer cells in vitro. These four cardiac hormones eliminate up to 86% of human small-cell lung carcinomas, 2/3rds of human breast cancers, and up to 80% of human pancreatic adenocarcinomas growing in athymic mice. Their anticancer mechanisms of action, after binding to specific receptors on cancer cells, include targeting the Rat sarcoma bound guanosine triphosphate (RAS) (95% inhibition)-mitogen activated protein kinase kinase 1/2 (MEK 1/2) (98% inhibition)-extracellular signal related kinase 1/2 (ERK 1/2) (96% inhibition) cascade in cancer cells. They also inhibit MAPK9, i.e. c-Jun-N¬-terminal kinase 2. They are dual inhibitors of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89%). One of the downstream targets of VEGF is Beta-catenin, which they reduce up to 88%. The WNT pathway is inhibited up to 68% and secreted Frizzled related protein 3 decreased up to 84% by the four cardiac hormones. AKT, a serine/threonine-protein kinase, is reduced up to 64% by the cardiac hormones. Signal transducer and activator of transcription 3 (STAT3), a final "switch" that activates gene expression that lead to malignancy, is decreased by up to 88% by the cardiac hormones. STAT3 is specifically decreased as they do not affect STAT1. There is cross-talk between the RAS-MEK 1/2-ERK 1/2 kinase cascade, VEGF, B-catenin, WNT, JNK and STAT pathways and each of these pathways is inhibited by the cardiac hormones.

PMID: 23533248 [PubMed - as supplied by publisher]

Related Articles

Non-Invasive Biomarkers in Exacerbations of Obstructive Lung Disease.

Respirology. 2013 Mar 25;

Authors: Warwick G, Thomas PS, Yates DH

Abstract
BACKGROUND AND OBJECTIVE: Current methods of diagnosing exacerbations of asthma and COPD shed little light on their aetiology or pathophysiology. Non-invasive diagnostic methods could be helpful in this setting. We aimed to define the inflammatory biomarker profile of subjects with obstructive lung diseases and to compare these with control subjects also with respiratory infections, using exhaled breath condensate (EBC) and induced sputum biomarker analysis. METHODS: Respiratory symptoms, EBC, induced sputum, and CRP were collected from subjects with exacerbations of asthma (n=28), exacerbations of COPD (n=29) and otherwise healthy controls with symptoms of respiratory tract infection (n=28). Subjects were tested again after recovery. EBC and induced sputum were analysed for protein, H2 O2 , IP-10, neopterin, IL-6, IL-8, LTB4 and TNF-α. Induced sputum cell counts and EBC pH were also analysed. RESULTS: EBC pH was significantly lower in exacerbation compared with recovery (5.54 0.07 vs 6.04 ± 0.08; p<0.001). The novel markers IP-10 and neopterin were significantly increased in induced sputum supernatant (pooled groups pre and post exacerbation: IP-10: 188.6 ± 102.1 vs 5.40 ± 1.28 pg/ml, p=0.006; neopterin: 15.81 ± 2.50 vs 5.38 ± 0.45 nmol/L, p<0.0001), as was TNF-α (137.8 ± 49.64 vs 71.56 ± 45.03 pg/ml, p=0.018). Few other biomarkers proved significantly different in exacerbation, although CRP was raised in peripheral blood. CONCLUSIONS: Non-invasive biomarker assessment may provide useful information in exacerbation of obstructive lung diseases, particularly sputum IP-10 and neopterin and EBC pH.

PMID: 23521049 [PubMed - as supplied by publisher]

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Role of long term antibiotics in chronic respiratory diseases.

Respir Med. 2013 Mar 19;

Authors: Suresh Babu K, Kastelik J, Morjaria JB

Abstract
Antibiotics are commonly used in the management of respiratory disorders such as cystic fibrosis (CF), non-CF bronchiectasis, asthma and COPD. In those conditions long-term antibiotics can be delivered as nebulised aerosols or administered orally. In CF, nebulised colomycin or tobramycin improve lung function, reduce number of exacerbations and improve quality of life (QoL). Oral antibiotics, such as macrolides, have acquired wide use not only as anti-microbial agents but also due to their anti-inflammatory and pro-kinetic properties. In CF, macrolides such as azithromycin have been shown to improve the lung function and reduce frequency of infective exacerbations. Similarly macrolides have been shown to have some benefits in COPD including reduction in a number of exacerbations. In asthma, macrolides have been reported to improve some subjective parameters, bronchial hyperresponsiveness and airway inflammation; however have no benefits on lung function or overall asthma control. Macrolides have also been used with beneficial effects in less common disorders such as diffuse panbronchiolitis or post-transplant bronchiolitis obliterans syndrome. In this review we describe our current knowledge the use of long-term antibiotics in conditions such as CF, non-CF bronchiectasis, asthma and COPD together with up-to-date clinical and scientific evidence to support our understanding of the use of antibiotics in those conditions.

PMID: 23522403 [PubMed - as supplied by publisher]

Early Antibiotic Discontinuation in Patients With Clinically Suspected Ventilator-Associated Pneumonia and Negative Quantitative Bronchoscopy Cultures.

Crit Care Med. 2013 Mar 22;

Authors: Raman K, Nailor MD, Nicolau DP, Aslanzadeh J, Nadeau M, Kuti JL

Abstract
OBJECTIVES:: Preliminary data suggest that antibiotic discontinuation in patients with negative quantitative bronchoscopy and symptom resolution will not increase mortality. Because our hospital algorithm for antibiotic discontinuation rules out ventilator-associated pneumonia in the setting of negative quantitative bronchoscopy cultures, we compared antibiotic utilization and mortality in empirically treated, culture-negative ventilator-associated pneumonia patients whose antibiotic discontinuation was early versus late. DESIGN:: Retrospective, observational cohort study. SETTING:: Eight hundred sixty-seven bed, tertiary care, teaching hospital in Hartford, CT. PATIENTS:: Eighty-nine patients with clinically suspected ventilator-associated pneumonia and a negative (<10 colony forming units/mL) quantitative bronchoscopy culture between January 2009 and March 2012. Early discontinuation patients (n = 40) were defined as those who had all antibiotic therapy stopped within one day of final negative culture report, whereas late discontinuation patients (n = 49) had antibiotics stopped later than one day. MEASUREMENTS:: Univariate analyses assessed mortality, antibiotic duration, and frequency of superinfections. Multivariate logistic regression was performed to assess the effect of early discontinuation on hospital mortality. RESULTS:: Patients had a mean ± SD Acute Physiology and Chronic Health Evaluation II score of 26.0 ± 6.0. Mortality was not different between early discontinuation (25.0%) and late discontinuation (30.6%) patients (p = 0.642). Antibiotic duration (days) was also not different for patients who died vs. those who survived (Median [interquartile range]: 3 [1-7.5] vs. 3 [1.75-6.25], respectively, p = 0.87), and when controlling for baseline characteristics and symptom resolution, only Acute Physiology and Chronic Health Evaluation II score was associated with hospital mortality on multivariate analyses. There were fewer superinfections (22.5% vs. 42.9%, p = 0.008), respiratory superinfections (10.0% vs. 28.6%, p = 0.036), and multidrug resistant superinfections (7.5% vs. 35.7%, p = 0.003), in early discontinuation compared with late discontinuation patients. CONCLUSIONS:: In this severely ill population with clinically suspected ventilator-associated pneumonia and negative quantitative bronchoalveolar lavage cultures, early discontinuation of antibiotics did not affect mortality and was associated with a lower frequency of MDR superinfections.

PMID: 23528805 [PubMed - as supplied by publisher]