Chromogranin A as a determinant of midgut carcinoid tumour volume

Kölby, Lars; Bernhardt, Peter; Swärd, Christina; Johanson, Viktor; Ahlman, Håkan; Forssell-Aronsson, Eva; Stridsberg, Mats; Wängberg, Bo; Nilsson, Ola

doi:10.1016/j.regpep.2004.03.017

Cited by 47 publications

(29 citation statements)

References 32 publications

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“…5). The mouse plasma levels of CgA in this MTC model were about 25 nM/g tumor, which was in the same range as in our midgut carcinoid model with GOT1 cells xenografted to nude mice (Kölby et al 2004). …”

Section: The Neuroendocrine Phenotype Of Got2 Cellssupporting

confidence: 70%

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis

Johanson

Ahlman²,

Bernhardt³

et al. 2007

Endocr Relat Cancer

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Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations in the RET protooncogene, resulting in constitutive activation of the RET tyrosine kinase. A substantial proportion of sporadic MTCs also have RET mutations, making the RET tyrosine kinase a potential therapeutic target in MTC. We have established a transplantable MTC in nude mice from a sporadic human MTC carrying a RET C634R mutation. Transplanted tumors had an exponential growth rate with an approximate doubling time of about 3 weeks, and expressed a neuroendocrine phenotype characteristic of MTC, e.g., expression of calcitonin, chromogranin A (CgA), synaptophysin, synaptic vesicle protein 2 (SV2), vesicular monoamine transporter-1 and -2, carcinoembryonic antigen, cytokeratin 8/18, epithelial cadherin, and neural cell adhesion molecule. Plasma calcitonin and CgA levels were elevated in tumor-bearing mice and correlated with tumor size. Cytogenetic analysis, including spectral karyotyping, confirmed the human origin of the xenografted tumors and demonstrated an abnormal, near triploid karyotype. Treatment of tumor-bearing nude mice with the tyrosine kinase inhibitor ZD6474, which specifically inhibits RET, epidermal growth factor receptor (EGFR), and vascular endothelium growth factor receptor (VEGFR) tyrosine kinases, resulted in a dose-dependent inhibition of tumor growth. Oral ZD6474 given once daily (250 mg/kg, 5 days/week) reduced tumor volume to 11% when compared with controls after 4 weeks. Our results show that this transplantable MTC, designated GOT2, represents a novel and useful model for studies of MTC and RET tyrosine kinase-dependent tumor growth.

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Section: The Neuroendocrine Phenotype Of Got2 Cellssupporting

confidence: 70%

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis

Johanson

Ahlman²,

Bernhardt³

et al. 2007

Endocr Relat Cancer

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“…Plasma CgA has also been reported to be significantly higher in metastatic gastroenteropancreatic endocrine tumors than in nonmetastatic tumors (26 ), and higher in patients with extensive SCLC than in patients with limited disease (27 ). CgA plasma concentrations have also been found to correlate with tumor weight in nude mice with xenografted human ileal carcinoid tumors (28 ). For some of the gastrointestinal neuroendocrine tumor patients with widespread, rapidly progressing disease the CgA PIA results seemed to enable better estimation of the tumor burden than the CgA(3403)assay results (results not shown).…”

Section: Discussionmentioning

confidence: 96%

Processing-Independent Quantitation of Chromogranin A in Plasma from Patients with Neuroendocrine Tumors and Small-Cell Lung Carcinomas

et al. 2007

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Background: Most neuroendocrine tumors express chromogranin A (CgA). The posttranslational processing of neuroendocrine proteins such as CgA is often specific for the individual tumor. To cope with this variability and improve tumor diagnosis, we developed a processing-independent analysis (PIA) method to measure the total CgA product. Methods: For PIA, samples underwent trypsin treatment followed by measurement of CgA by the "CgA(3403)" assay, in which the antiserum binds an epitope starting at amino acid 340 of CgA and including amino acid residues located in the C-terminal direction. The diagnostic accuracy of the CgA PIA and 3 sequencespecific assays for CgA were evaluated on plasma samples from patients with neuroendocrine tumors and small-cell lung carcinomas. Furthermore, we investigated whether the CgA plasma concentrations correlated with the tumor burden. Results: Size-exclusion chromatography of plasma showed that CgA immunoreactivity mainly consisted of high-molecular-weight forms, indicating that neuroendocrine tumors may secrete large amounts of poorly processed CgA. Accordingly, trypsination of plasma from 54 patients with neuroendocrine tumors or smallcell lung carcinomas increased the CgA(3403) immunoreactivity up to 500-fold. Both the CgA(3403) assay and the PIA measured significantly higher plasma concentrations in patients with very extensive disease than in patients with less widespread disease. The diagnostic

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“…Recent studies confirmed that the measurement of CgA levels in blood can also be used to diagnose and to monitor neuroendocrine tumours during treatment [6,10,14,[16][17][18].…”

Section: Introductionmentioning

confidence: 94%

Significance of plasma chromogranin A determination in neuroendocrine tumour (NET) diagnosis.

Donica

Malecha-Jędraszek²,

Strosławska³

et al. 2011

Folia Histochem Cytobiol.

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Chromogranin A as a determinant of midgut carcinoid tumour volume

Cited by 47 publications

References 32 publications

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis

Processing-Independent Quantitation of Chromogranin A in Plasma from Patients with Neuroendocrine Tumors and Small-Cell Lung Carcinomas

Significance of plasma chromogranin A determination in neuroendocrine tumour (NET) diagnosis.

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