Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

Sekiya, Keizo; Ghatei, Mohammad A.; Salahuddin, Mohammad; Bishop, Anne E.; Hamid, Qutayba; Itoh, Hiroshi; Polak, Julia M.; Bloom, Stephen R.

doi:10.1172/jci114089

Cited by 34 publications

(25 citation statements)

References 26 publications

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“…Increased CgB production has been found in neuroendocrine tumors, 28 and circulating CgB levels have been proposed as a potential biomarker in patients with neuroendocrine tumors. 14,29 The demonstration of increased circulating CgB levels during HF development suggests that CgB may potentially represent a novel cardiac biomarker. This notion is supported by regulation of circulating CgB levels in proportion to NYHA functional class.…”

Section: Discussionmentioning

confidence: 99%

“…29 In addition, circulating CgB levels were unaffected by PPI use, a medication currently recommended as a prophylactic measure in many patients with heart disease, 30 and with well-known stimulatory effects on CgA production. 13 Moreover, few other conditions are known to be associated with increased circulating CgB levels.…”

Section: Discussionmentioning

confidence: 99%

“…13 Moreover, few other conditions are known to be associated with increased circulating CgB levels. In fact, except for the rare neuroendocrine tumors, 14,29,31,32 confounding by other diseases does not seem to represent a major problem for use of CgB as a marker of cardiac status.…”

Section: Discussionmentioning

confidence: 99%

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Chromogranin B in Heart Failure

Røsjø

Husberg

Dahl

et al. 2010

Circ: Heart Failure

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Background-Chromogranin B (CgB) is a member of the granin protein family. Because CgB is often colocalized with chromogranin A (CgA), a recently discovered cardiac biomarker, we hypothesized that CgB is regulated during heart failure (HF) development. Methods and Results-CgB regulation was investigated in patients with chronic HF and in a post-myocardial infarction HF mouse model. Animals were phenotypically characterized by echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5. Key Words: heart failure Ⅲ molecular biology Ⅲ biological markers Ⅲ chromogranin B A dvances in treatment of acute coronary syndromes have reduced short-term mortality following acute myocardial infarction (MI), but at the cost of a higher incidence of post-MI heart failure (HF). 1 Improved pathophysiological understanding of HF and better tools for risk prediction and diagnostic purposes are therefore needed. 2 The cardiac biomarkers used routinely in clinical practice today are proteins specific to the diseased myocardium, either released during cell necrosis (cardiac specific troponins) 3 or secreted secondary to cardiomyocyte strain (B-type natriuretic peptide, BNP). 4 However, there is still a need for markers reflecting other pathophysiological processes in heart disease. 5 Thus, identifying new proteins regulated in the failing myocardium may potentially improve both the understanding of HF development and lead to the discovery of novel cardiac biomarkers. Clinical Perspective on p 511Chromogranin B (CgB) is a 50-kDa protein belonging to a group of acidic proteins called the granin protein family. 6 The most extensively studied and well-known member of the granin family is chromogranin A (CgA), a protein currently used clinically as a biomarker in patients with neuroendocrine tumors. 7 Recently, CgA has been shown to increase with the severity of HF 8 and to be an independent predictor of mortality in patients with acute coronary syndrome. 9 -11 Moreover, increased CgA production has been demonstrated in cardiomyocytes of the failing myocardium. 12 However, a confounding factor possibly reducing CgA's merit as a cardiac biomarker is the increase in CgA levels seen with the use of proton pump inhibitors (PPIs). 13 In contrast, CgB Methods Mouse Model of HFA permanent ligation of the left main coronary artery were performed in mice in the HF group, whereas sham-operated (sham) animals underwent the same procedure except ligation of the coronary artery. 16 Echocardiographic examination was performed 1 week after the primary operation. The criteria for including animals in the HF group have previously been validated. 17

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Chromogranin B in Heart Failure

Røsjø

Husberg

Dahl

et al. 2010

Circ: Heart Failure

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“…Elevated CgA levels were even more frequent (99%) in malignant carcinoid and gastroenteropancreatic tumours (99%) (Stridsberg et al 1995), with the highest levels seen in metastatic carcinoid (particularly midgut). Plasma CgB (and its 74-amino-acid fragment termed GAWK) is usually a better marker for benign insulin-producing tumours (Sekiya et al 1989, Yasuda et al 1993. Finally, multiple hormones may be secreted by some tumours (Wood et al 1983), and up to 62% have elevated gastrin despite only 30% presenting with peptic ulcer disease.…”

Section: General Markers For Neuroendocrine Tumoursmentioning

confidence: 99%

Neuroendocrine tumours.

Barakat¹,

Meeran²,

Bloom³

2004

Endocr Relat Cancer

Self Cite

209

111

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Neuroendocrine tumours are a heterogeneous group including, for example, carcinoid, gastroenteropancreatic neuroendocrine tumours, pituitary tumours, medullary carcinoma of the thyroid and phaeochromocytomas. They have attracted much attention in recent years, both because they are relatively easy to palliate and because they have indicated the chronic effect of the particular hormone elevated. As neuroendocrine phenotypes became better understood, the definition of neuroendocrine cells changed and is now accepted as referring to cells with neurotransmitter, neuromodulator or neuropeptide hormone production, dense-core secretory granules, and the absence of axons and synapses. Neuroendocrine markers, particularly chromogranin A, are invaluable diagnostically. Study of several neuroendocrine tumours has revealed a genetic etiology, and techniques such as genetic screening have allowed risk stratification and prevention of morbidity in patients carrying the particular mutation. Pharmacological therapy for these often slow-growing tumours, e.g. with somatostatin analogues, has dramatically improved symptom control, and radiolabelled somatostatin analogues offer targeted therapy for metastatic or inoperable disease. In this review, the diagnosis and management of patients with carcinoid, gut neuroendocrine tumours, multiple endocrine neoplasia types 1 and 2, and isolated phaeochromocytoma are evaluated.

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“…73 Plasma concentrations of CgB and its Cterminal fragment (GAWK) are elevated in patients with functioning pancreatic NEN. 45 In addition, measurement of both CgA and CgB in combination has been shown to increase detection of neuroendocrine tumours, although it was not determined if the increase was statistically significant. 73 Although the sensitivity and specificity of circulating CgA measurement in the biochemical diagnosis of NEN have been extensively studied, there has been less focus on CgB measurement and to date, there is one only published study on CART measurement.…”

Section: Diagnostic Use Of Cga Cgb and Cartmentioning

confidence: 99%

The biochemical utility of chromogranin A, chromogranin B and cocaine- and amphetamine-regulated transcript for neuroendocrine neoplasia

et al. 2013

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Neuroendocrine neoplasia (NEN) is a heterogeneous group of tumours and often represents a therapeutic challenge to clinicians. The peptides chromogranin A (CgA), chromogranin B (CgB) and cocaine-and amphetamine-regulated transcript (CART) are widely distributed throughout the neuroendocrine system. CgA and CgB have been used as general NEN biomarkers for many years, while CART has only recently been identified. Of these biomarkers, CgA is the most commonly used. However, circulating CgA concentrations exhibit considerable intra-individual biological variation, are altered by proton pump inhibitors (PPIs) and somatostatin analogues and are elevated in non-NEN malignancies. Therefore, interpretation of CgA results must be in the context of these confounding factors. The effects of treatment and non-NEN conditions on circulating CgB and CART concentrations are less well understood. CgB is less affected by impaired renal function and PPIs than CgA; while, circulating CART concentrations lack a diurnal variation in humans and are more reliable markers of pancreatic NEN malignancy than CgA. The utility of circulating CgA measurements in NEN prognosis, surveillance and disease recurrence has been widely investigated. However, the utility of CgB and CART in NEN management is yet to be elucidated. Further studies are needed to establish whether CgB and CART are useful alternatives to CgA.

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Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

Cited by 34 publications

References 26 publications

Chromogranin B in Heart Failure

Chromogranin B in Heart Failure

Neuroendocrine tumours.

The biochemical utility of chromogranin A, chromogranin B and cocaine- and amphetamine-regulated transcript for neuroendocrine neoplasia

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