Specific binding of 1,25-dihydroxycholecalciferol in human medullary thyroid carcinoma.
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ABSTRACT:
SUBMITTER: Freake HC
PROVIDER: S-EPMC1158568 | biostudies-other | 1982 Jul
REPOSITORIES: biostudies-other
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Project description:BackgroundLocally or widely metastatic medullary thyroid carcinoma (MTC) is difficult to treat, and therapeutic options are limited. Recently, kinase inhibitors have shown partial efficacy in this cancer, but there is a continued need for the development of novel therapeutics. Within this context, the Hedgehog (Hh) pathway has been implicated in several types of human tumors, and early clinical trials with Hh antagonists have validated Hh as a novel therapeutic target. For the first time, we evaluated Hh pathway activity in MTC, and examined the effect of Hh pathway perturbation in highly characterized MTC cell lines.MethodsWe examined immunohistochemical expression of the Hh signaling mediators Sonic Hedgehog (Shh) and Glioblastoma (Gli)2 in paraffin-embedded normal versus histologically characterized human MTC tissue. We examined pharmacologic disruption of Hh signaling in vitro using two established MTC cell lines (TT and MZ-CRC-1). Hh signaling was either pharmacologically activated (SAG) or inhibited (GDC-0449) in MTC cell lines; Hh activity was assessed by quantitative real-time polymerase chain reaction, Western blot analysis, and quantification of cellular growth and apoptotic activity.ResultsOur data showed increased expression of Hh signaling factors in human MTC compared to normal tissue. In vitro, activation of the Hh pathway resulted in increased expression of key Hh signaling components Smoothened (Smo) and Gli2. Conversely, inhibition of the Hh pathway decreased expression of these genes, leading to significantly reduced cellular growth and increased apoptosis.ConclusionsHedgehog signaling components are markedly upregulated in MTC. Hh pathway inhibitors have potential as novel therapeutic options in patients with metastatic and/or surgically unresectable MTC.
| S-EPMC3770247 | biostudies-literature
Project description:Medullary thyroid carcinoma (MTC) accounts for only 1-2% of thyroid cancers; however, metastatic MTC is a mortal disease with no cure. In this study, glycosphingolipids were isolated from human MTCs and characterized by mass spectrometry and binding of carbohydrate recognizing ligands. The tissue distribution of selected compounds was investigated by immunohistochemistry. The amount of acid glycosphingolipids in the MTCs was higher than in the normal thyroid glands. The major acid glycosphingolipid was the GD3 ganglioside. Sulfatide and the gangliosides GM3 and GD1a were also present. The majority of the complex non-acid glycosphingolipids had type 2 (Galβ4GlcNAc) core chains, i.e., the neolactotetraosylceramide, the Lex, H type 2 and x2 pentaosylceramides, the Ley and A type 2 hexaosylceramides, and the A type 2 heptaosylceramide. There were also compounds with globo (GalαGalβ4Glc) core, i.e., globotriaosylceramide, globotetraosylceramide, the Forssman pentaosylceramide, and the Globo H hexaosylceramide. Immunohistochemistry demonstrated an extensive expression av Ley in the MTC cells and also a variable intensity and prevalence of Globo H and Lex. One individual with multiple endocrine neoplasia type 2B expressed the Forssman determinant, which is rarely found in humans. This study of human MTC glycosphingolipids identifies glycans that could serve as potential tumor-specific markers.
| S-EPMC8509059 | biostudies-literature
Project description:Medullary thyroid cancer (MTC) accounts for less than 5% of all thyroid cancers, and it is a rare neuroendocrine tumor which derives from calcitonin-secreting thyroid C cells.Given the underlying mechanism involved in MTC remain unclear, the development and the specific pathways of MTC require further investigation.here we employed the application of TMT6plex-based LC-MS/MS to identify and analyze the novel differentially-expressed proteins(DEPs) from MTC patients, To our best knowledge, it is the first study to comprehensively investigate the molecular mechanisms of MTC by proteomics technology from Chinese MTC patients’ tissues, and these DEPs identified in our study will provide a better understanding of the underlying pathophysiology of MTC, as well as may provide potential therapeutic targets for patients with MTC.
2020-05-26 | PXD005898 | Pride
Project description:This study aims to investigate the microRNA profile in human medullary carcinoma tissue by microarray analysis and RT-qPCR. Matched tumor and adjacent normal tissue were obtained from 24 patients and analysed using human microRNA Microarray Kit Agilent, Differentially expressed miRNAs were validated by RT-qPCR using 37 other tumors samples (validation set), Associations of microRNA expression with clinicopathological items were studied
2014-12-15 | GSE40807 | GEO
Project description:The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.
| S-EPMC3328820 | biostudies-literature
Project description:BackgroundCalcitonin expression is a well-established marker for medullary thyroid carcinoma (MTC); yet the role of calcitonin receptor (CTR), its seven-transmembrane G-protein coupled receptor, remains to be established in C-cells derived thyroid tumors. The aim of this work was to investigate CTR expression in MTC and to correlate such expression with clinicopathological features in order to evaluate its possible role as a prognostic indicator of disease aggressiveness and outcome.MethodsCalcitonin receptor expression was analyzed in a series of 75 MTCs by immunohistochemistry, and by qPCR mRNA quantification in specimens from four patients. Statistical tests were used to evaluate the correlation between CTR expression and the clinicopathological and molecular characteristics of patients and tumors.ResultsCalcitonin receptor expression was detected in 62 out of 75 samples (82.7%), whereas 13 of the 75 samples (17.3%) were completely negative. CTR expression was significantly associated with expression of cytoplasmatic phosphatase and tensin homologue deleted on chromosome 10 and osteopontin, as well as with wild type RET/RAS genes and absence of tumor stroma, suggesting that CTR expression do not associate with clinicopathological signs of worse prognosis.DiscussionCalcitonin receptor expression appears to be associated in MTC with more differentiated status of the neoplastic cells.
| S-EPMC5600720 | biostudies-literature
Project description:This study was designed to retrospectively compare the sonographic features of medullary thyroid carcinoma (MTC) and the features of papillary thyroid carcinoma (PTC).A total of 97 patients with 127 MTCs between January 2000 and January 2016 and 107 consecutive patients with 132 PTCs were included in this study. Two radiologists retrospectively determined the sonographic features and compared the findings of MTCs and PTCs.Compared with the patients with PTCs, the patients with MTCs were older (46.9 years vs 42.9 years, P = 0.016) and the male proportion was higher (53.6% vs 33.6%, P = 0.005). Most of the MTCs had an irregular shape (72.4%), a length/width ratio <1 (75.6%), an unclear boundary (63.8%), no peripheral halo ring (93.7%), hypoechogenicity (96.9%), heterogeneous echotexture (76.4%), no cystic change (78.7%), calcification (63.8%), and hypervascularity (72.4%). There was no significant difference in the boundary, peripheral halo ring, echogenicity, and calcification between the MTCs and PTCs. However, compared with the PTCs, a larger size (2.2 vs 1.2 cm, P <0.001), a regular shape (27.6% vs 7.6%, P <0.001), a length/width ratio <1 (75.6% vs 51.5%, P<0.001), heterogeneous echotexture (76.4% vs 54.5%, P <0.001), cystic change (21.3 vs 8.3%, P = 0.005), and hypervascularity (72.4% vs 47.7%, P <0.001) were more frequent in the MTCs.The sonographic features with a higher likelihood of malignancy are common in MTCs, including a shape taller than the width, irregular infiltrative margins, an absent halo, hypoechogenicity, the presence of microcalcifications, and increased intranodular vascularity. However, MTCs tend to possess these suspicious sonographic features less often than PTCs, with the exception of hypervascularity, which was more frequent in MTCs.
| S-EPMC5266009 | biostudies-literature
Project description:This study aims to investigate the microRNA profile in human medullary carcinoma tissue by microarray analysis and RT-qPCR. Matched tumor and adjacent normal tissue were obtained from 24 patients and analysed using human microRNA Microarray Kit Agilent, Differentially expressed miRNAs were validated by RT-qPCR using 37 other tumors samples (validation set), Associations of microRNA expression with clinicopathological items were studied Matched tumor and adjacent normal frozen tissues were obtained from thyroid of 40 patients. Normal tissue (name with suffix S) and lesionnal tissue (name with suffix L) were hybridized on microarray.
2014-12-15 | E-GEOD-40807 | biostudies-arrayexpress
Project description:Multiple endocrine neoplasia type 2 is an autosomal dominant inherited syndrome caused by activating mutations in the RET proto-oncogene. The RETK666N DNA variant was previously reported in two isolated medullary thyroid carcinoma (MTC) cases, but no family studies are available, and its oncogenic significance remains unknown.The clinical features, genetic data, and family information of eight index MTC patients with a germline RETK666N variant were assessed.Four probands presented with MTC and extensive nodal metastasis, one with biopsy-confirmed distant metastasis. Two additional probands presented with localized disease. However, nodal status was not available. Of the final two probands, one had an incidental 1.5?mm MTC and C-cell hyperplasia uncovered after surgery for papillary thyroid carcinoma, and one had two foci of MTC (largest dimension 2.3?cm) detected after surgery for dysphagia. Genetic screening identified 16 additional family members carrying the K666N variant (aged 5-90 years), 11 of whom have documented evaluation for MTC. Of these, only two were found to have elevated basal serum calcitonin upon screening, and the remaining patients had calcitonin levels within the reference range. One patient who elected to have a thyroidectomy at 70 years of age was confirmed to have MTC. The other subject, 57 years old, elected surveillance. Four prophylactic thyroidectomies were performed, with one case of C-cell hyperplasia at 20 years and three cases that revealed normal pathology at ages 21, 30, and 30 years. None of the K666N DNA variant carriers had evidence of primary hyperparathyroidism or pheochromocytoma.From this case series, the largest such experience to date, it is concluded that the RETK666N variant is likely pathogenic and associated with low penetrance of MTC. However, the findings are insufficient to define its pathogenicity clearly and make firm recommendations for screening and treatment. Given the potential benefit associated with early detection of aberrant C-cell growth, and the noninvasive nature of genetic testing, "at risk" individuals should be screened, and if the K666N variant is identified, they should be managed using a personalized screening approach for detection of MTC.
| S-EPMC5175438 | biostudies-literature
Project description:BackgroundUnlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection.MethodsWe selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma.ResultsOne hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56).ConclusionPediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.
| S-EPMC9439710 | biostudies-literature