scholarly journals Primary high-grade calcitonin-negative neuroendocrine carcinoma of the thyroid: a very rare cancer

2018 ◽  
Vol 2018 ◽  
Author(s):  
Joseph A Chorny ◽  
John J Orrego ◽  
José Manuel Cameselle-Teijeiro
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Calcitonin Gene Related Peptide ◽  
Small Cell ◽  
Proliferation Index ◽  
List Type ◽  
Mrna Levels ◽  
High Grade ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Neuroendocrine Carcinomas

Summary Most medullary thyroid carcinomas (MTCs) are low grade and produce calcitonin. There are some calcitonin-negative MTCs that produce only calcitonin gene-related peptide (CGRP). Rarely, MTCs are negative for calcitonin and CGRP peptides, but contain their corresponding mRNAs. Primary thyroid neuroendocrine neoplasms other than MTCs are extremely rare. We describe a primary high-grade neuroendocrine carcinoma that was negative for CGRP and calcitonin at both the protein and mRNA levels. A 42-year-old woman presented with a rapidly enlarging thyroid mass replacing most of the left lobe and isthmus. A computed tomography-guided core-needle biopsy was performed. The tumor was composed of sheets of small-to-medium sized epithelial cells. The cells were immunoreactive for pancytokeratin, synaptophysin, CD56 and thyroid transcription factor-1, but negative for CK7, CK20, CD45, CD99, ERG, chromogranin A, thyroglobulin, calcitonin, CGRP and carcinoembryonic antigen. The Ki-67 proliferation index was ~90%. In situ hybridization was negative for calcitonin mRNA. The patient was initially diagnosed as having a small cell carcinoma. She was treated with cisplatin and etoposide (VP16), followed by radiation therapy. Given the excellent clinical course, the tumor was reviewed and reclassified as a high-grade neuroendocrine carcinoma (non-small-cell type). Heretofore, only a few other similar high-grade neuroendocrine tumors with negative markers of C-cell derivation have been reported. In our case, the patient is cancer free five years after diagnosis, but in the other cases, the outcome was poor. Learning points: There are neuroendocrine carcinomas of the thyroid that do not produce calcitonin or calcitonin gene-related peptide. This category of calcitonin-negative neuroendocrine carcinomas is heterogeneous, consisting of low- and high-grade tumors. The high-grade neuroendocrine carcinomas of the thyroid are rare and generally have a poor prognosis. They are divided into small cell and non-small cell or large cell types.

Calcitonin gene-related peptide in small cell lung carcinomas

1993 ◽  
Vol 39 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Søren Schifter ◽  
Lis Johannsen ◽  
Chris Bunker ◽  
Paul Brickell ◽  
Ellen Bork ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Carcinomas ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Retinoic acid repression of cell-specific helix-loop-helix-octamer activation of the calcitonin/calcitonin gene-related peptide enhancer.

1993 ◽  
Vol 13 (10) ◽  
pp. 6079-6088 ◽  
Author(s):  
T M Lanigan ◽  
L A Tverberg ◽  
A F Russo
Keyword(s):  
Retinoic Acid ◽  
Acid Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Retinoid X Receptor ◽  
Mrna Levels ◽  
Retinoic Acid Treatment ◽  
Enhancer Activity ◽  
Related Peptide ◽  
Helix Loop Helix ◽  
Calcitonin Gene

We have investigated the mechanism underlying repression of calcitonin/calcitonin gene-related peptide (CT/CGRP) gene expression by retinoic acid. Retinoic acid treatment of the CA77 thyroid C-cell line decreased CT/CGRP promoter activity two- to threefold, which correlates well with the decrease in calcitonin and CGRP mRNA levels. Repression is mediated through the nuclear retinoic acid receptors (RAR) on the basis of the retinoid specificity, the sensitivity of repression (half-maximal repression at 0.2 nM), and the additional repression caused by cotransfection of an alpha-RAR expression vector. The sequences required for retinoic acid repression were localized to an 18-bp element containing cell-specific enhancer activity. The enhancer binds helix-loop-helix (HLH) and octamer transcription factors that act synergistically to activate transcription. Retinoic acid repression requires both these factors since mutations in either motif resulted in the loss of repression. Furthermore, repression was observed only in cell lines containing enhancer activity. We have used electrophoretic mobility shift assays to show that repression does not involve direct DNA binding of RAR or RAR-retinoid X receptor heterodimers. Instead, repression appears to involve interactions with the stimulatory enhancer factors. Following retinoic acid treatment, there was a specific decrease in an enhancer complex containing both HLH and octamer proteins. Formation of the HLH-octamer complex was also specifically blocked by the addition of exogenous RAR-retinoid X receptor protein. These results demonstrate that RAR can repress CT/CGRP gene transcription by interfering with combinatorial activation by cell-specific HLH and octamer proteins.

scholarly journals Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression

Cephalalgia ◽  
2016 ◽  
Vol 39 (3) ◽  
pp. 333-341 ◽  
Author(s):  
Yan Wang ◽  
Anne E Tye ◽  
Junli Zhao ◽  
Dongqing Ma ◽  
Ann C Raddant ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Calcitonin Gene Related Peptide ◽  
Rat Cerebral Cortex ◽  
Mrna Levels ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Peptide Expression ◽  
Cortical Regions

Objective The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player in migraine. However, the mechanisms underlying the reported elevation of CGRP in the serum and cerebrospinal fluid of some migraineurs are not known. A candidate mechanism is cortical spreading depression (CSD), which is associated with migraine with aura and traumatic brain injury. The aim of this study was to investigate whether CGRP gene expression may be induced by experimental CSD in the rat cerebral cortex. Methods CSD was induced by topical application of KCl and monitored using electrophysiological methods. Quantitative PCR and ELISA were used to measure CGRP mRNA and peptide levels in discrete ipsilateral and contralateral cortical regions of the rat brain 24 hours following CSD events and compared with sham treatments. Results The data show that multiple, but not single, CSD events significantly increase CGRP mRNA levels at 24 hours post-CSD in the ipsilateral rat cerebral cortex. Increased CGRP was observed in the ipsilateral frontal, motor, somatosensory, and visual cortices, but not the cingulate cortex, or contralateral cortices. CSD also induced CGRP peptide expression in the ipsilateral, but not contralateral, cortex. Conclusions Repeated CSD provides a mechanism for prolonged elevation of CGRP in the cerebral cortex, which may contribute to migraine and post-traumatic headache.

INCREASE OF CALCITONIN GENE-RELATED PEPTIDE (CGRP) RELEASE AND mRNA LEVELS IN ENDOTOXIC RATS

Shock ◽  
1997 ◽  
Vol 7 (3) ◽  
pp. 225-229 ◽  
Author(s):  
Yueming Tang ◽  
Chide Han ◽  
Ronald R. Fiscus ◽  
Xian Wang
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Mrna Levels ◽  
Related Peptide ◽  
Cgrp Release ◽  
Calcitonin Gene

Calcitonin gene related peptide gene expression in collagen-induced arthritis

1995 ◽  
Vol 73 (7) ◽  
pp. 1015-1019 ◽  
Author(s):  
Eberhard Weihe ◽  
Donatus Nohr ◽  
Martin K.-H. Schäfer ◽  
Stefan Persson ◽  
Johanna Källström ◽  
...  
Keyword(s):  
Gene Expression ◽  
Motor Neurons ◽  
Calcitonin Gene Related Peptide ◽  
Motor Dysfunction ◽  
Mrna Levels ◽  
Related Peptide ◽  
Inflammatory Conditions ◽  
Systemic Corticosteroids ◽  
Calcitonin Gene ◽  
Peptide Gene

Changes in calcitonin gene related peptide (CGRP) gene expression in spinal motoneurons and dorsal root ganglia (DRG) of rats subjected to collagen II induced arthritis (CIA) were evaluated by semiquantitative in situ hybridization. The effects of systemic treatment with the corticosteroid budesonide on basal CGRP expression and on changes under inflammatory conditions were examined. CIA caused a significant increase in CGRP mRNA levels in DRG. Budesonide reduced the constitutive CGRP mRNA levels in DRG, compared with untreated control rats, and reversed the CIA-induced increase. In contrast, CIA caused a marked decrease of CGRP mRNA levels in motoneurons. Budesonide had no effect on constitutive CGRP mRNA levels in motoneurons and attenuated the decrease in CGRP mRNA levels in motoneurons of rats subjected to CIA. Thus, peripheral inflammation and systemic corticosteroids have differential effects on CGRP expression in sensory and motor neurons. This may be relevant for the pathophysiology and pharmacotherapy of chronic inflammatory pain and motor dysfunction in chronic arthritis.Key words: calcitonin gene related peptide, neuropeptides, sensory, spinal motoneuron, arthritis, glucocorticoids, pain.

scholarly journals Calcitonin gene-related peptide and muscle activity regulate acetylcholine receptor alpha-subunit mRNA levels by distinct intracellular pathways.

1987 ◽  
Vol 105 (3) ◽  
pp. 1337-1342 ◽  
Author(s):  
B Fontaine ◽  
A Klarsfeld ◽  
J P Changeux
Keyword(s):  
Muscle Activity ◽  
Mrna Level ◽  
Calcitonin Gene Related Peptide ◽  
Alpha Subunit ◽  
Mrna Levels ◽  
Subunit Mrna ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Actin Mrna ◽  
Alpha Actin

In cultured chicken myotubes, calcitonin gene-related peptide (CGRP), a peptide present in spinal cord motoneurons, increased by 1.5-fold the number of surface acetylcholine receptors (AChRs) and by threefold AChR alpha-subunit mRNA level without affecting the level of muscular alpha-actin mRNA. Cholera toxin (CT), an activator of adenylate cyclase, produced a similar effect, which did not add up with that of CGRP. In contrast, tetrodotoxin, a blocker of voltage-sensitive Na+ channels, elevated the level of AChR alpha-subunit mRNA on top of the increase caused by either CGRP or CT. 12-O-Tetradecanoyl phorbol-13-acetate (TPA), an activator of protein kinase C, markedly decreased the cell surface and total content of [125I]alpha BGT-binding sites and reduced the rate of appearance of AChR at the surface of the myotubes without reducing the level of AChR alpha-subunit mRNA. Moreover, TPA inhibited the increase of AChR alpha-subunit mRNA caused by tetrodotoxin without affecting that produced by CGRP or CT. Under the same conditions, TPA decreased the level of muscular alpha-actin mRNA and increased that of nonmuscular beta- and gamma-actins mRNA. These data suggest that distinct second messengers are involved in the regulation of AChR biosynthesis by CGRP and muscle activity and that these two pathways may contribute to the development of different patterns of AChR gene expression in junctional and extrajunctional areas of the muscle fiber.

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