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Concept: Chromogranin A

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Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers.

Concepts: Receptor antagonist, Receptor, Atrophic gastritis, Chromogranin A, Pernicious anemia, Stomach

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Chromogranin A (CgA) is the major soluble protein co-stored and co-released with catecholamines and can function as prohromone giving rise to several bioactive peptides. This review focuses on these molecules summarizing their physiological functions, their pathogenetic implications and their recent use as biomarkers in several pathological conditions. A thorough literature search of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized key-words such Chromogranin A, Vasostatin-1 and 2, Chromofungin, Chromacin, Pancreastatin, Catestatin, WE-14, Chromostatin, GE-25, Parastatin and Serpinin, and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular and the immune systems and by affecting the glucose or calcium homeostasis. Since some peptides exert similar effects, but other elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenetic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumours, but also in cardiovascular, inflammatory and neuropsychiatric diseases.

Concepts: Biology, Medicine, Chromogranin, Pathology, Chromogranin A, Physiology, Cancer, Immune system

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The neuroendocrine glycoprotein chromogranin A is a useful biomarker for stress in humans. Chromogranin A epitopes catestatin and vasostatin can be measured in dogs using radioimmunoassays. The objective of this study was to evaluate catestatin and vasostatin as canine stress biomarkers in a clinical setting. Blood and saliva were collected from 33 healthy dogs that were familiar with sampling procedures and the animal hospital environment (control group) and 30 healthy dogs that were unacquainted (stress group). During sampling, stress behavior was scored by the same observer using visual analog scale (VAS). Plasma was analyzed for catestatin and vasostatin, serum for cortisol, and saliva for catestatin. Differences between groups were analyzed using two-sample t-tests and P<0.05 was considered significant. Stress behavior VAS score in the control group was significantly lower than in the stress group during blood (P=0.002) and saliva (P=0.0009) sampling. Serum cortisol and saliva catestatin concentrations in the stress group were higher than the control group (P=0.003 and P<0.0001, respectively). Serum cortisol concentrations were correlated with those of saliva (r=0.34, P=0.04) and plasma catestatin (r=0.29, P=0.03). Plasma catestatin and vasostatin did not differ significantly between groups. In conclusion, concentrations of saliva catestatin, and serum cortisol, and stress behavior VAS scores were significantly higher in the stress group. The results indicate that saliva catestatin may be useful as a biomarker for acute psychological stress in dogs.

Concepts: Neuroendocrine, Stress, Chromogranin A, Scores

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Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up, and definition of treatment strategy. This review is focused on Chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack of standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects.

Concepts: Sensitivity and specificity, Chromogranin A, Marker, Diagnosis, Game theory

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Chromogranin A (CgA), a secretory protein released in the blood by neuroendocrine cells and neurons, is the precursor of various bioactive fragments involved in the regulation of the cardiovascular system, metabolism, innate immunity, angiogenesis, and tissue repair. After the original demonstration that circulating CgA can serve as a biomarker for a wide range of neuroendocrine tumors, several studies have shown that increased levels of CgA can be present also in the blood of patients with cardiovascular, gastrointestinal, and inflammatory diseases with, in certain cases, important diagnostic and prognostic implications. Considering the high structural and functional heterogeneity of the CgA system, comprising precursor and fragments, it is not surprising that the different immunoassays used in these studies led, in some cases, to discrepant results. Here, we review these notions and we discuss the importance of measuring total-CgA, full-length CgA, specific fragments, and their relative levels for a more thorough assessment of the pathophysiological function and diagnostic/prognostic value of the CgA system.

Concepts: Heart, Innate immune system, Circulatory system, Protein, Chromogranin A, Blood vessel, Blood, Immune system

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The relation between arrhythmias and stress is known. The aim of our current study was to elucidate whether plasma levels of previously described stress parameters are altered in highly symptomatic patients with atrial fibrillation (AF) per se and in patients undergoing ablation therapy by pulmonary vein isolation (PVI).

Concepts: Pulmonary artery, Endothelin, Lung, Chromogranin A, Pulmonary vein, Atrial fibrillation, Blood, Heart

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The discovery in 1953 of the chromaffin granules as co-storage of catecholamines and ATP was soon followed by identification of a range of uniquely acidic proteins making up the isotonic vesicular storage complex within elements of the diffuse sympathoadrenal system. In the mid-1960s, the enzymatically inactive, major core protein, chromogranin A was shown to be exocytotically discharged from the stimulated adrenal gland in parallel with the co-stored catecholamines and ATP. A prohormone concept was introduced when one of the main storage proteins collectively named granins was identified as the insulin release inhibitory polypeptide pancreastatin. A wide range of granin-derived biologically active peptides have subsequently been identified. Both chromogranin A and chromogranin B give rise to antimicrobial peptides of relevance for combat of pathogens. While two of the chromogranin A-derived peptides, vasostatin-I and pancreastatin, are involved in modulation of calcium and glucose homeostasis, respectively, vasostatin-I and catestatin are important modulators of endothelial permeability, angiogenesis, myocardial contractility, and innate immunity. A physiological role is now evident for the full-length chromogranin A and vasostatin-I as circulating stabilizers of endothelial integrity and in protection against myocardial injury. The high circulating levels of chromogranin A and its fragments in patients suffering from various inflammatory diseases have emerged as challenges for future research and clinical applications.

Concepts: Adrenal medulla, Hormone, Chromogranin, Chromogranin A, Glucose, Immune system, Epinephrine, Protein

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To investigate whether chromogranin A (CgA) is secreted from the heart into circulation.

Concepts: Chromogranin, Physiology, Chromogranin A, Secretion, Reptile, Cell, Mammal, Heart

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The granin family comprises altogether 7 different proteins originating from the diffuse neuroendocrine system and elements of the central and peripheral nervous systems. The family is dominated by three uniquely acidic members, namely chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). Since the late 1980ies it has become evident that these proteins are proteolytically processed, intragranularly and/or extracellularly into a range of biologically active peptides; a number of them with regulatory properties of physiological and/or pathophysiological significance. The aim of this comprehensive overview is to provide an up-to-date insight into the distribution and properties of the well established granin-derived peptides and their putative roles in homeostatic regulations. Hence, focus is directed to peptides derived from the three main granins, e.g. to the chromogranin A derived vasostatins, betagranins, pancreastatin and catestatins, the chromogranin B-derived secretolytin and the secretogranin II-derived secretoneurin (SN). In addition, the distribution and properties of the chromogranin A- derived peptides prochromacin, chromofungin, WE14, parastatin, GE-25 and serpinins, the CgB-peptide PE-11 and the SgII-peptides EM66 and manserin will also be commented on. Finally, the opposing effects of the CgA- derived vasostatin-I and catestatin and the SgII-derived peptide SN on the integrity of the vasculature, myocardial contractility, angiogenesis in wound healing, inflammatory conditions and tumors will be discussed.

Concepts: Peptide bond, Peptide, Amino acid, Chromogranin A, Physiology, Protein, Wound healing, Chromogranin

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Currently, serum chromogranin A is a well-established biomarker for pancreatic neuroendocrine tumors; however, other pancreatic diseases, oral use of a proton pump inhibitor and renal impairment can affect chromogranin A. Meanwhile, chromogranin B, belonging to the same granin family as chromogranin A, is not fully examined in these conditions. The present study aimed to evaluate the utility of chromogranin B as a pancreatic neuroendocrine tumor biomarker.

Concepts: Endocrine system, Cancer, Chromogranin A, Oncology, Pancreatic cancer, Neuroendocrine tumor