Skip to main content
NCBI home page
Journal of Diabetes and Metabolic Disorders logoLink to Journal of Diabetes and Metabolic Disorders
. 2021 Jan 7;23(2):1–9. doi: 10.1007/s40200-020-00702-1

Thyroid Cancer research at endocrinology and metabolism research institute (EMRI): a report of scientific activities between 2005 and 2020

Hilda Samimi 1, Nooshin Shirzad 1,2, Sayed Mahmoud Sajjadi-Jazi 3,1, Ramin Heshmat 4, Mahsa M Amoli 5, Mohammad Reza Mohajeri-Tehrani 1, Seyed Mohammad Tavangar 6, Bagher Larijani 1, Vahid Haghpanah 1,7,✉
PMCID: PMC11599522  PMID: 39610531

Abstract

Purpose

Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, has achieved many advances in the understanding of epidemiology, pathology, and molecular biology of thyroid cancer (TC). This paper will focus on published literature in the field of TC research at EMRI since its inception.

Methods

A comprehensive literature search of “Scopus”, “Web of Science (ISI)”, “PubMed”, and “SID” databases was done to identify TC-based studies in EMRI since 2005, using the predefined keywords.

Results

All the records were reviewed. Eventually, 46 articles that met the inclusion and exclusion criteria were considered. Timeline, characteristics, and summarized findings of the included most studies have been briefly described.

Conclusion

The main focus of the TC research at EMRI is to investigate genetic and epigenetic changes as well as the cellular and molecular aspects seen more frequently in TC patients, and find out how exactly these alterations lead to more aggressive TC behavior and resistance to the conventional treatment approaches in those patients.

Keywords: Papillary thyroid carcinoma, Follicular thyroid carcinoma, Medullary thyroid carcinoma, Anaplastic thyroid carcinoma, Endocrinology and metabolism research institute

Introduction

Thyroid cancer (TC) is the most frequent endocrine malignancy and has the highest growing incidence rate among different kinds of solid tumors in the United States [1]. Most of TCs can be treated with conventional surgical treatment followed by Radioiodine (RAI) and long-term thyroid-stimulating hormone (TSH)-suppressive therapy. However, nearly 5 % of TCs are RAI-resistant cases, which are locally advanced or metastatic with survival rate of less than 5 years [2, 3]. Currently, several advances exist in the diagnosis and treatment of TCs. These include molecular diagnostics, targeted therapies and more effective strategies for personalized medicine of TC patients. New molecular diagnostic methods and targeted therapies lead to specific or personalized treatment of TC patients [4]. Understanding the risk factors and biological mechanisms that cause resistance to conventional therapeutic approaches can be useful for recognizing patients who are unresponsiveness to treatment, decreasing the recurrence rate of disease, and also providing more appropriate therapeutic approach for these clinical challenges.

This paper will focus on the research activities, including epidemiology, pathology and molecular biology studies, specifically in the field of TC at Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, since its inception. Undoubtedly, beside the research purposes, a number of other scientific activities have been carried out in field of capacity building in the line of our research objectives, including PhD and MSc training and hosting various educational courses in the field of thyroid ultrasound as well as radiofrequency thermal ablation of thyroid nodules.

Methods

The main databases in English language including “Scopus”, “Web of Science (ISI)”, and “PubMed” as well as “SID” database for the papers published in Persian language were searched to identify TC-based studies in EMRI since 2005. Moreover, to find more evidence, other sources including “Google Scholar” were searched. Search keywords were: “Papillary Thyroid Carcinoma”, “Follicular Thyroid Carcinoma”, “Medullary Thyroid Carcinoma”, “Anaplastic Thyroid Carcinoma”, “Endocrinology and Metabolism Research Center”, “Endocrinology and Metabolism Research Institute”, and related words and phrases, Medical Subject Headings (MeSH) terms, EBSCO thesaurus terms and Emtree terms and their logical combinations.

The inclusion criteria were articles which related to TC research from 2005 to 2020. The exclusion criteria were defined as articles that were not related to TC, case report, letter to editor, and meeting abstract papers.

Results

All the identified papers were reviewed and after removing the duplicates and unrelated articles in the field of TC research, 46 articles that met the eligibility criteria were finally selected, most of which were briefly described in Table 1. Timeline, characteristics, and summarized findings of the included most studies are shown in this table.

Table 1.

Timeline, characteristics, and summary of the findings of the included studies

Year Title Main method(s) Summary of findings Ref.
2005 Primary thyroid malignancies in Tehran, Iran Descriptive epidemiology study Slightly increase in the incidence of TC in Tehran. The survival rate of patients was high. Survival time of men and women with TC in Tehran were similar. [5]
2006 Endocrine cancer in Iran: based on cancer registry system Descriptive epidemiology study Improving the intake of iodine in previously deficient populations was associated with an increase in the incidence of PTC. [6]
The frequency of histological forms of thyroid carcinoma was similar to what can be found in iodine-rich areas.
2006 Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma IHC Survivin is a potential candidate in the distinction between FTA and FTC. [7]
2007 Vitamin D receptor gene polymorphisms in patients with thyroid cancer RFLP There are no correlation between the polymorphisms located at 3′ end of vitamin D receptor gene and risk of TC. [8]
2009 Associations between HLA-C alleles and papillary thyroid carcinoma HLA typing HLA-C alleles are predisposing factors in PTC in Iranian population. [9]
2009 Expression of EGFRvIII in thyroid carcinoma: immunohistochemical study by camel antibodies Antibody production Diagnostic value of smaller heavy chain camel antibodies against EGFRvIII in thyroid neoplasms. [10]
Western-blot
IHC
2009 Immunohistochemical analysis of nm23 protein expression in thyroid papillary carcinoma and follicular neoplasm IHC There is no relationship between the expression of nm23 protein and patientsʼ sex and age. [11]
nm23 is not a beneficial biomarker for assessing the invasion of DTC or the distinction between FTC and FTA.
2009 Prevalence of BRAFV600E mutation in Iranian patients with papillary thyroid carcinoma: A single-center study RFLP The BRAFV600E mutation is detected in 72% of classical variant of PTC and 100% of tall cell variant of PTC. [12]
There is no significance association between BRAFV600E mutation prevalence and sex, age, lymph node metastasis, and extrathyroid extension.
2010 HLA-DR association in papillary thyroid carcinoma HLA typing HLA-DRB1*04 is predisposing factor in PTC in Iranian population. [13]
2011 Molecular analysis of the RET proto-oncogene key exons in patients with medullary thyroid carcinoma: A comprehensive study of the iranian population Sequencing 17.6% of sporadic cases of medullary thyroid carcinoma (MTC) carried a germ-line mutation in RET gene. [14]
Most mutations detected in the families occurred in cysteine codons.
Germ-line mutation carriers have an earlier age onset of MTC versus the sporadic ones.
2011 Evaluating clinical practice guidelines developed for the management of thyroid nodules and thyroid cancers and assessing the reliability and validity of the AGREE instrument Mixed methods (Systematic search, Secondary data analysis…) ‘Scope and purpose’ and ‘clarity and presentation’ clinical guidelines have the highest domain scores based on the AGREE instrument. [15]
‘Rigor of development’ and ‘clarity and presentation’ acquired the highest correlations with overall evaluation scores.
2011 Qualitative and quantitative promoter hypermethylation patterns of the P16, TSHR, RASSF1A and RARβ2 genes in papillary thyroid carcinoma Combined bisulfite restriction analysis Promoter hypermethylation of P16, TSHR and RASSF1A genes play important role in PTC pathogenesis. [16]
2011 Incidence of second primary malignancies during a long-term surveillance of patients with differentiated thyroid carcinoma in relation to radioiodine treatment Retrospective cohort study The overall rate of second primary malignancies was not increased following a minimum interval of 3 years from the first I131 therapy. The probability of this occurrence may be profoundly increased in cases who had received a cumulative dose of I131 more than 40 GBq (1.08 Ci). [17]
2012 Multifaceted suppression of aggressive behavior of thyroid carcinoma by all-trans retinoic acid induced re-differentiation Cell culture All-trans retinoic acid treatment could inhibit the aggressive manners of TC and/or potentiate the effect of arsenic trioxide chemotherapy medicine. [18]
Proliferation assay
C ratio and morphological analysis
Colony formation assay
qRT-PCR
Radioimmunoassay
2012 Survivin gene polymorphism association with papillary thyroid carcinoma Genotyping Survivin gene polymorphism correlated with the risk of PTC in Iranian population. [19]
2012 Expression of matrix metalloproteinase-2, but not caspase-3, facilitates distinction between benign and malignant thyroid follicular neoplasms IHC The potential value of measuring MMP2 expression in discrimination between FTA and FTC. [20]
2013 Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors IHC Evaluating the expression of MMP2 in PTC patients may be a useful marker in predicting of tumor aggressiveness. [21]
There is no significant correlation between Caspase-3 expression and vascular invasion in patients with PTC.
2013 MicroRNAs networks in thyroid cancers: focus on miRNAs related to the fascin Narrative reviews Increased miRNAs expression in 32% of TCs. [22]
Decreased miRNAs expression in 38% of TCs.
2013 Essential genes in thyroid cancers: focus on fascin Narrative reviews The importance of P53, RAS, RET, BRAF, PPARγ and Fascin genes in TC. [23]
2014 Characterization of wild-type and mutated RET proto- oncogene associated with familial medullary thyroid cancer Sequencing Mutation-based stability shift findings in RET showed that C.G2901A (P.C634Y) and C.G2901T (P.C634F) mutations were destabilizing, hence the stabilizing factor was C.G2251A (P.G691S) mutations. [24]
Modeling
Molecular docking
Simulation
The importance of the simultaneous analysis of the mutations in improved chemotherapy resistance and designing new anticancer drugs.
2014 The beneficial effects of valproic acid in thyroid cancer are mediated through promoting redifferentiation and reducing stemness level: an in vitro study Cell culture assay Redifferentiation of ATC cell line and reduction of stemness properties of PTC cell line using Valproic acid. [25]
Cytotoxic assay
C ratio and morphological analysis
Colony formation assay
qRT-PCR
Hoechst 33342 staining
2016 Antisense-miR-21 enhances differentiation/ apoptosis and reduces cancer stemness state on anaplastic thyroid cancer Cell culture miR-21 has a role in stemness properties, growth, differentiation, and apoptosis. [26]
Virus packaging and transduction
Apoptosis assay
Cell cycle assay
qRT-PCR
IRMA
2016 Cancer stem-like cell behavior in anaplastic thyroid cancer: A challenging dilemma Cell culture This study reconfirmed the concept of CSC as origin of ATC. [27]
MACS
qRT-PCR
2017 Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer Meta-analysis Among RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1 tumor suppressor genes, promoter methylation of SLC5A8 and CDH1 is associated with the risk of TC development. [28]
2017 Precision medicine approach to anaplastic thyroid cancer: advances in targeted drug therapy based on specific signaling pathways Narrative reviews To appoint the best strategy for ATC therapy, personalized medicine can use different data such as a patient’s genetics and clinical background. [29]
2018 Decreased apolipoprotein A4 and increased complement component 3 as potential markers for papillary thyroid carcinoma: A proteomic study Proteomics study Proteomic study showed that the apolipoprotein A4 decreased and complement component 3 increased in serum of patients with PTC. [30]
2018 Serum-based metabolic alterations in patients with papillary thyroid carcinoma unveiled by non-targeted 1H-NMR metabolomics approach 1H-NMR Serum metabolites are different between malignant and benign thyroid nodules. [31]
2019 Promoter methylation of four tumor suppressor genes in human papillary thyroid carcinoma MS-HRM assay Among SLC5A8, RASSF1, MGMT, and DNMT1 tumor suppressor genes, promoter methylation of SLC5A8, RASSF1, and MGMT is different between PTC and goiter tissue samples. [32]
2019 Circulating ctDNA methylation quantification of two DNA methyl transferases in papillary thyroid carcinoma Bisulfite treatment A number of ctDNA promoter regions of MGMT and DNMT1 genes are hypermethylated in plasma and tissue samples of PTC patients. [33]
MS-HRM assay
The methylation status of ctDNA promoter regions of MGMT and DNMT1 genes and tissue DNA are related to each other.
2019 Transcript-level regulation of MALAT1-mediated cell cycle and apoptosis genes using dual MEK/Aurora kinase inhibitor “BI-847325” on anaplastic thyroid carcinoma 3D cell culture Targeting the regulatory network of lncRNA MALAT1 may be a more effective therapeutic approach for ATC. [34]
qRT-PCR
2019 The role of ATP-binding cassette transporters in the chemoresistance of anaplastic thyroid cancer: a systematic review Systematic review ABC transporters are the major determinants of chemotherapy resistance in ATC. [35]
2019 Determination of ATP-competitive inhibitor drug toxicity in anaplastic thyroid cancer based on cell characteristics and three-dimensional cell culture 3D cell culture The 3D cell culture systems are useful for obtaining the most appropriate anticancer drug with the most effective dose in ATC cell lines. [36]
Cytotoxic assay
CFSE staining
2020 Investigation of promoter methylation of FSCN1 gene and FSCN1 protein expression in differentiated thyroid carcinomas Bisulfite treatment FSCN1 promoter is hypomethylated in patients with PTC while the methylation status is not altered in FTC. [37]
IHC
Hypomethylation of FSCN1 promoter in PTC does not promote to overexpression of FSCN1.
2020 Hypermethylated RASSF1 and SLC5A8 promoters alongside BRAFV600E mutation as biomarkers for papillary thyroid carcinoma qRT-PCR Plasma cfDNAs originate from tumor tissue because the pattern of methylation and mutation of BRAFV600E in plasma and tissue DNA is the same. [38]
Bisulfite treatment
MS-HRM assay
The BRAFV600E cfDNA mutation is the best predictive biomarker for PTC.
Hypermethylation in the proximal promoter regions to the RASSF1 and SLC5A8 genes has sensitivity and specificity for discriminating between PTC and benign thyroid nodules.
2020 Gut microbiome and radioiodine-refractory papillary thyroid carcinoma pathophysiology Mini review GM might be related to RAIR-PTC through different molecular mechanisms associated with the NIS regulation as the main factor in I− uptake. [39]
2020 Molecular mechanisms of long non-coding RNAs in anaplastic thyroid cancer: A systematic review Systematic review LncRNAs such as GAS5, CASC2, and MIR22HG may serve as prognosis markers. [40]
LncRNAs Klhl14-AS, PCA3, and HOTAIRM1 may act as molecular therapeutic targets.
2020 Bioinformatic study on effect of Xanthohumol as bioactive compound of hop in the inhibition of the MAPK/ERK pathway in thyroid cancer Evaluation of physicochemical, phamacokinetic, and pharmacodynamic characteristics Xanthohumol acts as an inhibitor of MAPK/ERK pathway in TC cells. [41]
Xanthohumol, as a natural small molecule, does not have the potential to develop resistance in TC cells.
Molecular docking
Open in a new tab

Abbreviations: 1H-NMR, hydrogen-1 nuclear magnetic resonance; 3D, three-dimensional; ABC, ATP binding cassette; AGREE, Appraisal of Guidelines Research and Evaluation; ATC, anaplastic thyroid carcinoma; BRAF, v-Raf murine sarcoma viral oncogene homolog B; CASC2, cancer susceptibility candidate 2; CDH1, cadherin 1; cfDNA, circulating cell-free DNA; CFSE, 5,6-carboxyfluorescein N-hydroxysuccinimidyl ester; CSC, cancer stem cell; ctDNA, circulating tumor DNA; Ci, cuire; DAPK, death associated protein kinase; DNMT1, DNA methyltransferase 1; DTC, differentiated thyroid cancer; EGFRvIII, epithelial growth factor receptor variant III; FSCN1, fascin actin-bundling protein 1; FTA, follicular thyroid adenoma; FTC, follicular thyroid carcinoma; GAS5, growth arrest special 5; GBq, gigabecquerel; GM, gut microbiome; HLA-C, major histocompatibility complex class I C; HLA-DR, major histocompatibility complex class II DR; HLA-DRB1, major histocompatibility complex class II DR beta1; HOTAIRM1, HOX antisense intergenic RNA myeloid 1;IHC, immunohistochemical; I−, iodine; LncRNA, long non-coding RNA; IRMA, immunoradiometric assay; Klhl14, kelch like family member 14; MACS, magnetic-activated cell sorting; MALAT1, metastasis associated lung adenocarcionoma transcript 1; MEK, mitogen-activated protein kinase kinase 1; MEN 2A, multiple endocrine neoplasia type 2A; MGMT, O-6-methylguanine-DNA methyltransferase; MIR22HG, MIR22 host gene; miRNA, micro RNA; MMP2, matrix metallopeptidase 2; MRI, magnetic resonance imaging; MS-HRM, methylation-sensitive high resolution melting; MTC, medullary thyroid carcinoma; NIS, sodium/iodide symporter; P16, cyclin dependent kinase inhibitor 2A; P53, tumor protein P53; PPARγ, peroxisome proliferator activated receptor gamma; PCA3, prostate cancer antigen 3; PTC, papillary thyroid carcinoma; PTEN, phosphatase and tensin homolog; RAIR, radioiodine-refractory; RARβ2, retinoic acid receptor beta; RASSF1A, Ras association domain family member 1; RFLP, restriction fragment length polymorphism; qRT-PCR, quantitative real-time polymerase chain reaction; RAS association domain family member 1; RET, ret. proto-oncogene; SLC5A8, solute carrier family 5 member 8; TC, thyroid cancer; TSHR, thyroid stimulating hormone receptor

Discussion

In recent years, the main focus of the TC research at EMRI is to investigate molecular changes seen more frequently in TC patients, and find out how exactly these alterations lead to more aggressive TC behavior and resistance to the conventional treatment approaches in those patients [42–50]. However, at the beginning of our research we studied in the fields of pathology [7] and epidemiology [5, 6, 51, 52].

The incidence rate of TC is increasing in Iranian population [53]. Well-differentiated TC is the most frequent endocrine malignancy and ranks as 7th cancer diagnosed in females [54]. Although the majority of well-differentiated TC patients become disease-free following conventional treatments, 20% of TC patients have local or regional recurrent disease, and 5 % develop distant metastases [55, 56]. Due to lack of the effective treatment for the patients with poorly-differentiated or undifferentiated TCs, these patients have a poor prognosis with survival rate of less than 5 years.

The mechanisms by which genetic and epigenetic changes induce tumorigenesis, progression, and unresponsiveness to treatment in some TC cases are not fully understood. The information we have learned from the mechanisms involved in the initiation and progression of TCs could lead directly to more efficient treatment of TC patients, especially those with aggressive types of TC including radioiodine-refractory differentiated thyroid cancers (RAIR-DTC) and anaplastic thyroid carcinoma (ATC). Our findings revealed that HLA-C alleles and HLA-DRB1*04 are predisposing factors in papillary thyroid carcinoma (PTC) patients in Iranian population [9, 13]. We also investigated the correlation of survivin gene polymorphism with the risk of PTC in Iranian population [19]. In another study, we showed that the hypermethylation of P16, TSHR, and RASSF1A gene promoter may have an important role in PTC pathogenesis [16].

In addition, the TC research group at EMRI is focused on translational research in TC. For instance, TC research team is looking for the diagnostic molecular markers including gene expression classification and gene mutation panels to improve accuracy in distinguishing between benign and malignant disease such as follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC) [20].

As part of the advancement of precision medicine in cancer therapy, we hypothesized that attempts to efficiently treat advanced and aggressive TCs, such as RAIR-DTC and ATC, based on the genetic variation of each patient, could enhance therapeutic approaches [29].

Some of the studies, carried out during this period, were mentioned above. Evaluation of TC research at EMRI showed that there is a well-established research plan for investigation of clinical challenges in the fields of diagnosis, treatment, and prognosis of different types of TC.

To this end, the TC research group has done projects in various basic studies including cellular and molecular fields. In addition, this group plans to focus more on Na+/I− symporter (NIS), as the main factor in iodine (I−) uptake and response to RAI therapy, as well as the signaling pathways related to cancer stem cell properties, as important molecular mechanisms in the development and progression of poorly-differentiated/undifferentiated TC.

We hope to use these studies as well as the results of future findings to identify patients based on molecular testing and to treat patients with advanced and aggressive TC with novel targeted therapies directed at the specific genetic mutations.

Acknowledgements

In Memory of Professor Mohammad Hasan Bastan Hagh.

Prof. Mohammad Hasan Bastan Hagh was the founder of the Thyroid Research Group of Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences and left long-lasting scientific attainments.

May his soul rest in peace and he will be cherished in our memories forever.

The authors would like to thanks Dr. Mahmood Naderi for his helpful suggestions and advice. Also, the authors are grateful to Ms. Rasha Atlasi for literature search.

Abbreviations

1H-NMR

hydrogen-1 nuclear magnetic resonance

3D

three-dimensional

ABC

ATP binding cassette

AGREE

Appraisal of Guidelines Research and Evaluation

ATC

anaplastic thyroid carcinoma

BRAF

v-Raf murine sarcoma viral oncogene homolog B

CASC2

cancer susceptibility candidate 2

CDH1

cadherin 1

cfDNA

circulating cell-free DNA

CFSE

5,6-carboxyfluorescein N-hydroxysuccinimidyl ester

CSC

cancer stem cell

ctDNA

circulating tumor DNA

Ci

cuire

DAPK

death associated protein kinase

DNMT1

DNA methyltransferase 1

DTC

differentiated thyroid cancer

EGFRvIII

epithelial growth factor receptor variant III

EMRI

endocrinology and metabolism research institute

FSCN1

fascin actin-bundling protein 1

FTA

follicular thyroid adenoma

FTC

follicular thyroid carcinoma

GAS5

growth arrest special 5

GBq

gigabecquerel

GM

gut microbiome

HLA-C

major histocompatibility complex class I C

HLA-DR

major histocompatibility complex class II DR

HLA-DRB1

major histocompatibility complex class II DR beta1

HOTAIRM1

HOX antisense intergenic RNA myeloid 1

IHC

immunohistochemical

I−

iodine

LncRNA

long non-coding RNA

IRMA

immunoradiometric assay

Klhl14

kelch like family member 14

MACS

magnetic-activated cell sorting

MALAT1

metastasis associated lung adenocarcionoma transcript 1

MEK

mitogen-activated protein kinase kinase 1

MEN 2A

multiple endocrine neoplasia type 2A

MGMT

O-6-methylguanine-DNA methyltransferase

MIR22HG

MIR22 host gene

miRNA

micro RNA

MMP-2

matrix metallopeptidase 2

MRI

magnetic resonance imaging

MS-HRM

methylation-sensitive high resolution melting

MTC

medullary thyroid carcinoma

NIS

sodium/iodide symporter

P16

cyclin dependent kinase inhibitor 2A

P53

tumor protein P53

PPARγ

peroxisome proliferator activated receptor gamma

PCA3

prostate cancer antigen 3

PTC

papillary thyroid carcinoma

PTEN

phosphatase and tensin homolog

RAI

radioiodine

RAIR

radioiodine-refractory

RAIR-DTC

radioiodine-refractory differentiated thyroid cancer

RARβ2

retinoic acid receptor beta

RASSF1A

Ras association domain family member 1

RFLP

restriction fragment length polymorphism

qRT-PCR

quantitative real-time polymerase chain reaction; RAS association domain family member 1

RET

ret. proto-oncogene

SLC5A8

solute carrier family 5 member 8

TC

thyroid cancer

TSH

thyroid-stimulating hormone

TSHR

thyroid-stimulating hormone receptor.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Competing interests

The authors declare that they have no conflict of interest.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Jung CK, Little MP, Lubin JH, Brenner AV, Wells SA, Sigurdson AJ, et al. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab. 2014;99(2):E276–E85. [DOI] [PMC free article] [PubMed]
  • 2.Fugazzola L, Elisei R, Fuhrer D, Jarzab B, Leboulleux S, Newbold K, et al. 2019 European thyroid association guidelines for the treatment and follow-up of advanced radioiodine-refractory thyroid Cancer. Eur Thyroid J. 2019;8(5):227–45. [DOI] [PMC free article] [PubMed]
  • 3.Aashiq M, Silverman DA, Na’ara S, Takahashi H, Amit M. Radioiodine-refractory thyroid Cancer: molecular basis of Redifferentiation therapies, management, and novel therapies. Cancers. 2019;11(9):1382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin. 2013;63(6):373–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Larijani B, Mohagheghi MA, Bastanhagh MH, Mosavi-Jarrahi AR, Haghpanah V, Tavangar SM, et al. Primary thyroid malignancies in Tehran, Iran. Med Princ Pract. 2005;14(6):396–400. [DOI] [PubMed]
  • 6.Haghpanah V, Soliemanpour B, Heshmat R, Mosavi-Jarrahi A, Tavangar S, Malekzadeh R, et al. Endocrine cancer in Iran: based on cancer registry system. Indian J Cancer. 2006;43(2):80–5. [DOI] [PubMed]
  • 7.Haghpanah V, Shooshtarizadeh P, Heshmat R, Larijani B, Tavangar SM. Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma. Appl Immunohistochem Mol Morphol. 2006;14(4):422–5. [DOI] [PubMed] [Google Scholar]
  • 8.Haghpanah V, Ghaffari SH, Rahimpour P, Abbasi A, Saeedi M, Pak H, et al. Vitamin D receptor gene polymorphisms in patients with thyroid cancer. Gene Ther Mol Biol. 2007;11(2):299–304. [Google Scholar]
  • 9.Haghpanah V, Khalooghi K, Adabi K, Amiri P, Tavangar SM, Amirzargar A, et al. Associations between HLA-C alleles and papillary thyroid carcinoma. Cancer Biomarkers. 2009;5(1):19–22. [DOI] [PubMed] [Google Scholar]
  • 10.Omidfar K, Moinfar Z, Sohi AN, Tavangar SM, Haghpanah V, Heshmat R, et al. Expression of EGFRvIII in thyroid carcinoma: immunohistochemical study by camel antibodies. Immunol Investig. 2009;38(2):165–80. [DOI] [PubMed] [Google Scholar]
  • 11.Tabriz HM, Adabi K, Lashkari A, Heshmat R, Haghpanah V, Larijani B, et al. Immunohistochemical analysis of nm23 protein expression in thyroid papillary carcinoma and follicular neoplasm. Pathol Res Prac. 2009;205(2):83–7. [DOI] [PubMed] [Google Scholar]
  • 12.Mohammadi-Asl J, Larijani B, Khorgami Z, Tavangar SM, Haghpanah V, Mehdipour P. Prevalence of BRAFV600E mutation in Iranian patients with papillary thyroid carcinoma: a single-center study. J Appl Sci. 2009;9(19):3593–7. 10.3923/jas.2009.3593.3597. [Google Scholar]
  • 13.Amoli MM, Yazdani N, Amiri P, Sayahzadeh F, Haghpanah V, Tavangar SM, et al. HLA-DR association in papillary thyroid carcinoma. Dis Markers. 2010;28(1):49–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Alvandi E, Akrami SM, Chiani M, Hedayati M, Nayer BN, Tehrani MRM, et al. Molecular analysis of the RET proto-oncogene key exons in patients with medullary thyroid carcinoma: a comprehensive study of the iranian population. Thyroid. 2011;21(4):373–82. 10.1089/thy.2010.0267. [DOI] [PubMed] [Google Scholar]
  • 15.Irani S, Rashidian A, Yousefi-Nooraie R, Soltani A. Evaluating clinical practice guidelines developed for the management of thyroid nodules and thyroid cancers and assessing the reliability and validity of the AGREE instrument. J Eval Clin Pract. 2011;17(4):729–36. 10.1111/j.1365-2753.2010.01561.x. [DOI] [PubMed] [Google Scholar]
  • 16.Mohammadi-asl J, Larijani B, Khorgami Z, Tavangar SM, Haghpanah V, Kheirollahi M, et al. Qualitative and quantitative promoter hypermethylation patterns of the P16, TSHR, RASSF1A and RARβ2 genes in papillary thyroid carcinoma. Med Oncol. 2011;28(4):1123–8. [DOI] [PubMed] [Google Scholar]
  • 17.Fallahi B, Adabi K, Majidi M, Fard-Esfahani A, Heshmat R, Larijani B, et al. Incidence of second primary malignancies during a long-term surveillance of patients with differentiated thyroid carcinoma in relation to radioiodine treatment. Clin Nucl Med. 2011;36(4):277–82. [DOI] [PubMed] [Google Scholar]
  • 18.Malehmir M, Haghpanah V, Larijani B, Ahmadian S, Alimoghaddam K, Heshmat R, et al. Multifaceted suppression of aggressive behavior of thyroid carcinoma by all-trans retinoic acid induced re-differentiation. Mol Cell Endocrinol. 2012;348(1):260–9. [DOI] [PubMed] [Google Scholar]
  • 19.Yazdani N, Sayahpour FA, Haghpanah V, Amiri P, Shahrabi-Farahani M, Moradi M, et al. Survivin gene polymorphism association with papillary thyroid carcinoma. Pathol Res Pract. 2012;208(2):100–3. [DOI] [PubMed] [Google Scholar]
  • 20.Sanii S, Saffar H, Tabriz HM, Qorbani M, Haghpanah V, Tavangar SM. Expression of matrix metalloproteinase-2, but not caspase-3, facilitates distinction between benign and malignant thyroid follicular neoplasms. Asian Pac J Cancer Prev. 2012;13(5):2175–8. [DOI] [PubMed] [Google Scholar]
  • 21.Saffar H, Sanii S, Emami B, Heshmat R, Panah VH, Azimi S, et al. Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors. Pathol Res Pract. 2013;209(3):195–9. 10.1016/j.prp.2012.06.011. [DOI] [PubMed] [Google Scholar]
  • 22.Samimi H, Ghadami M, Khashayar P, Soleimani M, Larijani B, Haghpanah V. MicroRNAs networks in thyroid cancers: focus on miRNAs related to the fascin. J Diabetes Metab Disord. 2013;12(1):31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Samimi H, Ghadami M, Khashayar P, Soleimani M, Larijani B, Haghpanah V. Essential genes in thyroid cancers: focus on fascin. J Diabetes Metab Disord. 2013;12(1):32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Masbi MH, Mohammadiasl J, Galehdari H, Ahmadzadeh A, Tabatabaiefar MA, Golchin N, et al. Characterization of wild-type and mutated RET proto-oncogene associated with familial medullary thyroid cancer. Asian Pac J Cancer Prev. 2014;15:2027–33. [DOI] [PubMed] [Google Scholar]
  • 25.Haghpanah V, Malehmir M, Larijani B, Ahmadian S, Alimoghaddam K, Heshmat R, et al. The beneficial effects of valproic acid in thyroid cancer are mediated through promoting redifferentiation and reducing stemness level: an in vitro study. J Thyroid Res. 2014;2014:1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Haghpanah V, Fallah P, Tavakoli R, Naderi M, Samimi H, Soleimani M, et al. Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness state on anaplastic thyroid cancer. Tumor Biol. 2016;37(1):1299–308. [DOI] [PubMed] [Google Scholar]
  • 27.Haghpanah V, Fallah P, Naderi M, Tavakoli R, Soleimani M, Larijani B. Cancer stem-like cell behavior in anaplastic thyroid cancer: a challenging dilemma. Life Sci. 2016;146:34–9. [DOI] [PubMed] [Google Scholar]
  • 28.Khatami F, Larijani B, Heshmat R, Keshtkar A, Mohammadamoli M, Teimoori-Toolabi L et al. Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer. 2017;12(9):e0184892. 10.1371/journal.pone.0184892. [DOI] [PMC free article] [PubMed]
  • 29.Samimi H, Fallah P, Sohi AN, Tavakoli R, Naderi M, Soleimani M, et al. Precision medicine approach to anaplastic thyroid cancer: advances in targeted drug therapy based on specific signaling pathways. Acta Medica Iranica. 2017:200–8. [PubMed]
  • 30.Yekta RF, Oskouie AA, Tavirani MR, Mohajeri-Tehrani MR, Soroush AR. Decreased apolipoprotein A4 and increased complement component 3 as potential markers for papillary thyroid carcinoma: a proteomic study. Int J Biol Markers. 2018;33(4):455–62. 10.1177/1724600818787752. [DOI] [PubMed] [Google Scholar]
  • 31.Yekta RF, Tavirani MR, Oskouie AA, Mohajeri-Tehrani MR, Soroush AR, Baghban AA. Serum-based metabolic alterations in patients with papillary thyroid carcinoma unveiled by non-targeted 1H-NMR metabolomics approach. Iran J Basic Med Sci. 2018;21(11):1140–7. 10.22038/ijbms.2018.30375.7323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Khatami F, Larijani B, Heshmat R, Nasiri S, Saffar H, Shafiee G, et al. Promoter methylation of four tumor suppressor genes in human papillary thyroid carcinoma. Iran J Pathol. 2019;14(4):290–9. 10.30699/IJP.2019.94401.1922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Khatami F, Teimoori-Toolabi L, Heshmat R, Nasiri S, Saffar H, Mohammadamoli M, et al. Circulating ctDNA methylation quantification of two DNA methyl transferases in papillary thyroid carcinoma. J Cell Biochem. 2019;120(10):17422–37. 10.1002/jcb.29007. [DOI] [PubMed] [Google Scholar]
  • 34.Samimi H, Haghpanah V, Irani S, Arefian E, Sohi AN, Fallah P, et al. Transcript-level regulation of MALAT1-mediated cell cycle and apoptosis genes using dual MEK/Aurora kinase inhibitor “BI-847325” on anaplastic thyroid carcinoma. Daru. 2019;27:1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Abbasifarid E, Sajjadi-Jazi SM, Beheshtian M, Samimi H, Larijani B, Haghpanah V. The role of ATP-binding cassette transporters in the Chemoresistance of anaplastic thyroid Cancer: a systematic review. Endocrinology. 2019;160(8):2015–23. [DOI] [PubMed] [Google Scholar]
  • 36.Samimi H, Haghpanah V, Irani S, Fallah P, Arefian E, Soleimani M. Determination of ATP-competitive inhibitor drug toxicity in anaplastic thyroid Cancer based on cell characteristics and three-dimensional cell culture. Modares Journal of Biotechnology. 2019;10(3):503–9. [Google Scholar]
  • 37.Mahdiannasser M, Haghpanah V, Damavandi E, Kabuli M, Tavangar SM, Larijani B, et al. Investigation of promoter methylation of FSCN1 gene and FSCN1 protein expression in differentiated thyroid carcinomas. Mol Biol Rep. 2020;47(3):2161–9. 10.1007/s11033-020-05315-8. [DOI] [PubMed] [Google Scholar]
  • 38.Khatami F, Larijani B, Heshmat R, Nasiri S, Haddadi-Aghdam M, Teimoori-Toolabi L, et al. Hypermethylated RASSF1 and SLC5A8 promoters alongside BRAFV600E mutation as biomarkers for papillary thyroid carcinoma. J Cell Physiol. 2020;235(10):6954–68. 10.1002/jcp.29591. [DOI] [PubMed] [Google Scholar]
  • 39.Samimi H, Haghpanah V. Gut microbiome and radioiodine-refractory papillary thyroid carcinoma pathophysiology. Trends Endrocrinol Metab. 2020;31:627–30. [DOI] [PubMed] [Google Scholar]
  • 40.Samimi H, Sajjadi-Jazi SM, Seifirad S, Atlasi R, Mahmoodzadeh H, Faghihi MA, et al. Molecular mechanisms of long non-coding RNAs in anaplastic thyroid cancer: a systematic review. Cancer Cell Int. 2020;20(1):1–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Gholizadeh Siahmazgi Z, Irani S, Ghiaseddin A, Fallah P, Haghpanah V. BIOINFORMATIC study on effect of XANTHOHUMOL as bioactive compound of hop in the inhibition of the MAPK/ERK pathway in thyroid cancer. Iranian Journal of Diabetes and Metabolism. 2020;19(4):225–33. [Google Scholar]
  • 42.Farrokhi Yekta R, Rezaie Tavirani M, Arefi Oskouie A, Mohajeri-Tehrani MR, Soroush AR. The metabolomics and lipidomics window into thyroid cancer research. Biomarkers. 2017;22(7):595–603. 10.1080/1354750X.2016.1256429. [DOI] [PubMed] [Google Scholar]
  • 43.Khatami F, Tavangar SM. Circulating tumor DNA (ctDNA) in the era of personalized cancer therapy. J Diabetes Metab Disord. 2018;17(1):19–30. 10.1007/s40200-018-0334-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Khatami F, Tavangar SM. Genetic and epigenetic of medullary thyroid cancer. Iran Biomed J. 2018;22(3):142–50. 10.22034/ibj.22.3.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Khatami F, Tavangar SM. A review of driver genetic alterations in thyroid cancers. Iran J Pathol. 2018;13(2):125–35. 10.30699/ijp.13.2.125. [PMC free article] [PubMed] [Google Scholar]
  • 46.Khatami F, Tavangar SM. Liquid biopsy in thyroid cancer: new insight. Int J Hematol Oncol Stem Cell Res. 2018;12(3):234–47. [PMC free article] [PubMed] [Google Scholar]
  • 47.Khatami F, Larijani B, Nasiri S, Tavangar SM. Liquid biopsy as a minimally invasive source of thyroid cancer genetic and epigenetic alterations. Int J Mol Cell Med. 2019;8:19–29. 10.22088//IIJMCM.BUMS.8.2.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Khatami F, Larijani B, Nikfar S, Hasanzad M, Fendereski K, Tavangar SM. Personalized treatment options for thyroid cancer: current perspectives. Pharmgenomics Pers Med. 2019;12:235–45. 10.2147/PGPM.S181520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Khatami F, Payab M, Sarvari M, Gilany K, Larijani B, Arjmand B, et al. Oncometabolites as biomarkers in thyroid cancer: a systematic review. Cancer Manag Res. 2019;11:1829–41. 10.2147/CMAR.S188661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Homayouni M, Mohammad Arabzadeh SA, Nili F, Razi F, Amoli MM. Evaluation of the presence of Epstein-Barr virus (EBV) in Iranian patients with thyroid papillary carcinoma. Pathol Res Pract. 2017;213(7):854–6. 10.1016/j.prp.2017.01.020. [DOI] [PubMed] [Google Scholar]
  • 51.Larijani B, Aghakhani S, Khajeh-Dini H, Baradar-Jalili R. Clinico-pathological features of thyroid cancer as observed in five referral hospitals in Iran. Acta Oncol. 2003;42(4):334–7. [DOI] [PubMed] [Google Scholar]
  • 52.Farzadfar F, Peykari N, Larijani B, Rahimzadeh S, Rezaei-Darzi E, Saeedi MS. A comprehensive study on national and sub national trend in thyroid cancer prevalence in the iranian population, 1990–2010. Iranian Journal of Diabetes and Metabolism. 2016;15(2):91–100. [Google Scholar]
  • 53.Mohammadi E, Aminorroaya A, Fattahi N, Azadnajafabad S, Rezaei N, Farzi Y, et al. Epidemiologic pattern of cancers in Iran; current knowledge and future perspective. J Diabetes Metab Disord. 2020. 10.1007/s40200-020-00654-6. [DOI] [PMC free article] [PubMed]
  • 54.Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future Oncol. 2010;6(11):1771–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Song H-J, Qiu Z-L, Shen C-T, Wei W-J, Luo Q-Y. Pulmonary metastases in differentiated thyroid cancer: efficacy of radioiodine therapy and prognostic factors. Eur J Endocrinol. 2015;173(3):399–408. [DOI] [PubMed] [Google Scholar]
  • 56.Sampson E, Brierley JD, Le LW, Rotstein L, Tsang RW. Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis. Cancer. 2007;110(7):1451–6. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Diabetes and Metabolic Disorders are provided here courtesy of Springer

RESOURCES