Reduced MHC class II expression in medullary thyroid cancer identifies patients with poor prognosis

2021 ◽  
Author(s):  
Xianhui Ruan ◽  
Jiaoyu Yi ◽  
Linfei Hu ◽  
Jingtai Zhi ◽  
Yu Zeng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mhc Class Ii ◽  
Medullary Thyroid Cancer ◽  
Immune Escape ◽  
Class Ii ◽  
In Vitro Assays ◽  
Blood Leukocytes ◽  
Medullary Thyroid ◽  
Mhc Ii

Increasing body of recent studies determining the expression of tumor-specific major histocompatibility complex (MHC) class II protein support its potential role in several malignancies but little is known in human medullary thyroid cancer (MTC). Here we report the expression of MHC-II and its clinicopathologic and prognostic relevance in MTC patients. Immunohistochemistry staining revealed a significant reduction in tumor cell specific MHC-II expression in a higher AJCC stage and its poor prognostic correlation with human MTC development. Further statistical analysis identified the low MHC-II expression as a significant and independent risk factor for MTC recurrence and patient survival. Moreover, in vitro studies showed that the MHC-II expression was remarkably increased by RET inhibitors, which were prescribed to treat advanced MTC. Similarly, inhibitors blocking the MAPK/ERK and AKT/mTOR pathways also augmented MHC-II expression, suggesting their implications in RET-MHC-II signaling axis. Importantly, in vitro assays manifested enhanced peripheral blood leukocytes-mediated cytotoxicity in MTC cells treated with RET inhibitors, which were partially alleviated by HLA knock-down. Together, our study demonstrates that low MHC-II expression levels may serve as a prognostic biomarker for aggressive diseases in MTC patients and indicates that RET activation may promote MTC immune escape through down-regulating MHC-II expression.

scholarly journals Interleukin-2 and Lanreotide in the Treatment of Medullary Thyroid Cancer: In Vitro and In Vivo Studies

2013 ◽  
Vol 98 (10) ◽  
pp. E1567-E1574 ◽  
Author(s):  
Giovanni Vitale ◽  
Giovanni Lupoli ◽  
Rosario Guarrasi ◽  
Annamaria Colao ◽  
Alessandra Dicitore ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Interleukin 2 ◽  
In Vivo Studies ◽  
Medullary Thyroid

scholarly journals Localization of CaSR Antagonists in CaSR-expressing Medullary Thyroid Cancer

2013 ◽  
Vol 98 (11) ◽  
pp. E1722-E1729 ◽  
Author(s):  
Haiming Ding ◽  
Adlina Mohd Yusof ◽  
Shankaran Kothandaraman ◽  
Motoyasu Saji ◽  
Chaojie Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Nude Mice ◽  
Medullary Thyroid Cancer ◽  
Antagonistic Activity ◽  
Parathyroid Glands ◽  
Human Embryonic Kidney Cells ◽  
Medullary Thyroid ◽  
Calcium Stimulation

Objective: Image-based localization of medullary thyroid cancer (MTC) and parathyroid glands would improve the surgical outcomes of these diseases. MTC and parathyroid glands express high levels of calcium-sensing receptor (CaSR). The aim of this study was to prove the concept that CaSR antagonists specifically localize to CaSR-expressing tumors in vivo. Design: We synthesized two isomers of a known CaSR calcilytic, Calhex 231, and four new analogs, which have a favorable structure for labeling. Their antagonistic activity was determined using immunoblots demonstrating decreased ERK1/2 phosphorylation after calcium stimulation in human embryonic kidney cells overexpressing CaSR. Compound 9 was further radiolabeled with 125I and evaluated in nude mice with and without heterotransplanted xenografts of MTC cell lines, TT and MZ-CRC-1, that do and do not express CaSR, respectively. Results: Two newly synthesized compounds, 9 and 11, exhibited better antagonistic activity than Calhex 231. The half-life of 125I-compound 9 in nude mice without xenografts was 9.9 hours. A biodistribution study in nude mice bearing both tumors demonstrated that the uptake of radioactivity in TT tumors was higher than in MZ-CRC-1 tumors at 24 hours: 0.39 ± 0.24 vs 0.18 ± 0.12 percentage of injected dose per gram of tissue (%ID/g) (P = .002), with a ratio of 2.25 ± 0.62. Tumor-to-background ratios for TT tumors, but not MZ-CRC-1 tumors, increased with time. Tumor-to-blood values increased from 2.02 ± 0.52 at 1 hour to 3.29 ± 0.98 at 24 hour (P = .015) for TT tumors, and 1.7 ± 0.56 at 1 hour to 1.48 ± 0.33 at 24 hour (P = .36) for MZ-CRC-1 tumors. Conclusions: Our new CaSR antagonists specifically inhibit CaSR function in vitro, preferentially localize to CaSR-expressing tumors in vivo, and therefore have the potential to serve as scaffolds for further development as imaging pharmaceuticals.

CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity in medullary thyroid cancer in vitro and in vivo

2014 ◽  
Vol 393 (1-2) ◽  
pp. 56-64 ◽  
Author(s):  
Alessandro Antonelli ◽  
Guido Bocci ◽  
Concettina La Motta ◽  
Silvia Martina Ferrari ◽  
Poupak Fallahi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid

scholarly journals A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1441 ◽  
Author(s):  
Aayushi Srivastava ◽  
Beiping Miao ◽  
Diamanto Skopelitou ◽  
Varun Kumar ◽  
Abhishek Kumar ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Germline Mutation ◽  
Medullary Thyroid Cancer ◽  
Current Knowledge ◽  
Wild Type ◽  
Medullary Thyroid ◽  
Wild Type Counterpart ◽  
In Silico Analyses ◽  
Protection Of Telomeres 1

Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole-genome sequencing study of five families with occurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here, we report in silico analyses and in vitro experiments on a novel germline variant (p.V29L) in the highly conserved oligonucleotide/oligosaccharide binding domain of the Protection of Telomeres 1 (POT1) gene in one of the families. The results showed a reduction in telomere-bound POT1 levels in the mutant protein as compared to its wild-type counterpart. HEK293T cells carrying POT1 p.V29L showed increased telomere length in comparison to wild-type cells, suggesting that the mutation causes telomere dysfunction and may play a role in predisposition to NMTC in this family. While one germline mutation in POT1 has already been reported in a melanoma-prone family with prevalence of thyroid cancers, we report the first of such mutations in a family affected solely by NMTCs, thus expanding current knowledge on shelterin complex-associated cancers.

Antineoplastic activity of the multitarget tyrosine kinase inhibitors CLM3 and CLM94 in medullary thyroid cancer in vitro

Surgery ◽  
2014 ◽  
Vol 156 (5) ◽  
pp. 1167-1176 ◽  
Author(s):  
Silvia Martina Ferrari ◽  
Poupak Fallahi ◽  
Concettina La Motta ◽  
Guido Bocci ◽  
Alda Corrado ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Antineoplastic Activity ◽  
Medullary Thyroid

Interferon alpha and rapamycin inhibit the growth of carcinoid and medullary thyroid cancer in vitro

2014 ◽  
Vol 66 (4) ◽  
pp. 624-629 ◽  
Author(s):  
Ewelina Motylewska ◽  
Hanna Lawnicka ◽  
Magdalena Kowalewicz-Kulbat ◽  
Paulina Sicinska ◽  
Agata Niedziela ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Interferon Alpha ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid

CALCITONIN HETEROGENEITY IN LUNG CANCER AND MEDULLARY THYROID CANCER

1978 ◽  
Vol 89 (1) ◽  
pp. 89-99 ◽  
Author(s):  
Kenneth L. Becker ◽  
Richard H. Snider ◽  
Omega L. Silva ◽  
Charles F. Moore
Keyword(s):  
Thyroid Cancer ◽  
Cancer Patients ◽  
Medullary Thyroid Cancer ◽  
Gel Filtration ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Fraction I ◽  
Bronchogenic Cancer

ABSTRACT An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Endogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I (≧ 30 000 molecular weight (MW)) to fraction V (~ 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i. e. fractions I and II A). Following in vitro incubation of the serum, the typical large MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.

Guideline for in vivo- and in vitro procedures for thyroid diseases (version 2)

2003 ◽  
Vol 42 (03) ◽  
pp. 109-115 ◽  
Author(s):  
M. Dietlein ◽  
J. Dressler ◽  
F. Grünwald ◽  
K. Joseph ◽  
B. Leisner ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Tsh Receptor ◽  
Definitive Treatment ◽  
Functional Assay ◽  
Chronic Lymphocytic Thyroiditis ◽  
Assay Sensitivity ◽  
Medullary Thyroid

SummaryThe version 2 of the guideline for diagnostic standards of thyroid disorders is an update of the guideline published in 1999 and describes standards of in vitro and in vivo procedures. The following statements are modified: In vitro procedures: When measurement of the TSH-receptor antibodies is indicated, the guideline recommends the use of a second generation assay (recombinant human TSH-receptor as antigen). The functional assay sensitivity for the measurement of thyroglobulin should reach a value ≤1 ng/ml. Moleculargenetic tests (RET proto-oncogen) are indicated in patients with a newly diagnosed medullary thyroid cancer and in the relatives of patients with hereditary medullary thyroid cancer. In vivo procedures: The sonographic examination should use a probe with a frequency of at least 7.5 MHz. Indications for the thyroid scintigraphy: nodule size ≥1 cm in diameter, autonomous goitre/nodule with clinical or subclinical hyperthyroidism, necessity of a differentiation between Graves’ disease and chronic lymphocytic thyroiditis, therapy control after a definitive treatment and – in individual cases – the follow-up of untreated autonomous nodules.

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