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Cancers
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Molecular Advances and Targeted Therapy in Asian Thyroid Practice
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Molecular Advances and Targeted Therapy in Asian Thyroid Practice

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 14278

Special Issue Editor

Dr. Kennichi Kakudo

E-Mail Website
Guest Editor
Department of Pathology and Thyroid Disease Center, Izumi-City General Hospital, Izumi 594-0073, Japan
Interests: thyroid; thyroiditis; thyroid carcinomas; borderline tumors; diagnosis; classification; prognosis; immunohistochemistry; FNA cytology; pathology; genetic cancers

Special Issue Information

Dear Colleagues,

Thyroid follicular cell carcinomas (papillary carcinoma (PTC), follicular carcinoma (FTC), poorly differentiated carcinoma, and anaplastic carcinoma) are the most common malignancy of endocrine organs, and their incidence has increased rapidly around the world. We are now fighting against them in multiple battlefields, such as introducing the borderline/precursor tumor category in the thyroid tumor classification system to reduce overdiagnosis and overtreatment of low-risk thyroid carcinomas, which has impacted current thyroid practice significantly. In this Special Issue, “Molecular Advances and Targeted Therapy in Asian Thyroid Practice”, we would like to focus on the second battlefield, which is how to manage high-risk thyroid carcinomas and advanced-stage thyroid carcinomas. Although these are rare in thyroid practice, they are clinically significant carcinomas (aggressive variant PTCs, angioinvasive FTCs, poorly differentiated carcinomas, and advanced-stage thyroid carcinomas). Early detection and sufficient cancer treatments (total thyroidectomy and radioactive iodine treatment) are mandatory. Furthermore, recent advances in the molecular mechanism of thyroid carcinoma progression have created a new field in thyroid practice. Effective targeted therapies have been introduced for the treatment of clinically significant thyroid carcinomas. It is our pleasure to invite you to this Special Issue. Please join us with your perspectives on how to accurately identify high-risk thyroid carcinomas and how to approach them.

Dr. Kennichi Kakudo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • thyroid carcinoma
  • high-risk carcinoma
  • advanced stage
  • targeted therapy
  • borderline tumor
  • diagnosis
  • gene
  • pathology

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Published Papers (5 papers)

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Research

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13 pages, 4804 KiB  
Article
Molecular Pathological Characteristics of Thyroid Follicular-Patterned Tumors Showing Nodule-in-Nodule Appearance with Poorly Differentiated Component
by Mayu Ueda, Katsuya Matsuda, Hirokazu Kurohama, Zhanna Mussazhanova, Yerkezhan Sailaubekova, Hisayoshi Kondo, Tomoki Shimizu, Nami Takada, Yuki Matsuoka, Chieko Otsubo, Shinya Sato, Hiroyuki Yamashita, Atsushi Kawakami and Masahiro Nakashima
Cancers 2022, 14(15), 3577; https://doi.org/10.3390/cancers14153577 - 22 Jul 2022
Cited by 6 | Viewed by 2014
Abstract
Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 [...] Read more.
Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 (53BP1) is a DNA damage response (DDR) molecule that rapidly localizes at DNA double-strand breaks. Using dual-color immunofluorescence with Ki-67, the profile of 53BP1 expression is shown to be significantly altered during diverse tumorigenesis. In this study, we aimed to elucidate the malignant potential of PDc at the molecular level. We analyzed the profile of 53BP1 expression and NRAS codon 61 and TERT-promoter (TERT-p) mutations in 16 cases of TFTs showing NN with PDc compared to 30 adenomatous goiters, 31 follicular adenomas, 15 minimally invasive follicular carcinomas (FCs), and 11 widely invasive FC cases. Our results revealed that the expression level of abnormal type 53BP1 and incidence of NRAS and TERT-p mutations in PDc were comparable to FCs, suggesting a malignant potential. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations. Full article
(This article belongs to the Special Issue Molecular Advances and Targeted Therapy in Asian Thyroid Practice)
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14 pages, 5926 KiB  
Article
Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß
by Xinpei Wang, Xiujie Cui, Qian Zhao, Feifei Sun, Ru Zhao, Tingting Feng, Shaofeng Sui, Bo Han and Zhiyan Liu
Cancers 2022, 14(11), 2772; https://doi.org/10.3390/cancers14112772 - 2 Jun 2022
Cited by 9 | Viewed by 2237
Abstract
Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays [...] Read more.
Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß. Full article
(This article belongs to the Special Issue Molecular Advances and Targeted Therapy in Asian Thyroid Practice)
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15 pages, 4378 KiB  
Article
Targeting IGF2BP2 Promotes Differentiation of Radioiodine Refractory Papillary Thyroid Cancer via Destabilizing RUNX2 mRNA
by Ri Sa, Rui Liang, Xian Qiu, Ziyan He, Zhiyan Liu and Libo Chen
Cancers 2022, 14(5), 1268; https://doi.org/10.3390/cancers14051268 - 1 Mar 2022
Cited by 11 | Viewed by 2659
Abstract
N6-methyladenosine (m6A) regulators play an important role in multiple biological and pathological processes of radioiodine refractory papillary thyroid cancer (RR-PTC). However, the function of m6A regulators in differentiation of RR-PTC remains unclear. In this study, online data, clinical samples, and RR-PTC cell lines [...] Read more.
N6-methyladenosine (m6A) regulators play an important role in multiple biological and pathological processes of radioiodine refractory papillary thyroid cancer (RR-PTC). However, the function of m6A regulators in differentiation of RR-PTC remains unclear. In this study, online data, clinical samples, and RR-PTC cell lines (K1 and TPC1) were used to identify the m6A regulators that contributed to the differentiation of RR-PTC. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was found to be associated with thyroid-specific genes in online data analyses, and metastatic PTCs with high expression of IGF2BP2 were prone to be 131I-nonavid in clinical analyses. Furthermore, targeting IGF2BP2 increased 125I uptake in RR-PTC cell lines and enhanced the sodium/iodide symporter (NIS) expression. Mechanistically, IGF2BP2 bound to the m6A modification site of runt-related transcription factor 2 (RUNX2) 3′-UTR and enhanced the RUNX2 mRNA stability. Moreover, RUNX2 could bind to the promoter region of NIS to block the differentiation of RR-PTC. Together, these results demonstrated that IGF2BP2 represents a diagnostic marker for RR-PTC, suggesting a novel differentiation therapeutic strategy of targeting IGF2BP2. Full article
(This article belongs to the Special Issue Molecular Advances and Targeted Therapy in Asian Thyroid Practice)
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Review

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19 pages, 14536 KiB  
Review
Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada
by Mohannad Rajab, Richard J. Payne, Véronique-Isabelle Forest and Marc Pusztaszeri
Cancers 2022, 14(17), 4140; https://doi.org/10.3390/cancers14174140 - 26 Aug 2022
Cited by 20 | Viewed by 3737
Abstract
In the past few decades, molecular characterization of thyroid cancer has made significant progress and is able to identify thyroid-cancer-related molecular markers that can then be applied clinically for improved decision making. The aim of this review is to provide a general overview [...] Read more.
In the past few decades, molecular characterization of thyroid cancer has made significant progress and is able to identify thyroid-cancer-related molecular markers that can then be applied clinically for improved decision making. The aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, present several molecular tests, and discuss the clinical applications of identifying these markers supported by the clinical experience of several high-volume thyroid cancer specialists at the McGill university hospitals in Montreal, Canada. Our group experience showed that molecular testing can reclassify more than half of the patients with indeterminate thyroid nodules (Bethesda III and IV) into benign and spare these patients from unnecessary diagnostic surgery. Furthermore, it can help optimize the initial management in thyroid cancers with no evidence of high risk of recurrence of disease preoperatively. While routine molecular testing is not firmly established for thyroid FNA specimens that are suspicious or positive for malignancy (Bethesda V and VI), knowledge of a thyroid nodule’s molecular risk group profile in such cases, together with its clinical and radiologic features, can help select the optimal surgical options (lobectomy versus upfront total thyroidectomy and central neck dissection), as demonstrated by our studies. Full article
(This article belongs to the Special Issue Molecular Advances and Targeted Therapy in Asian Thyroid Practice)
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Other

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11 pages, 2029 KiB  
Commentary
Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice
by Kennichi Kakudo
Cancers 2022, 14(3), 812; https://doi.org/10.3390/cancers14030812 - 5 Feb 2022
Cited by 15 | Viewed by 2680
Abstract
Histopathological diagnosis of papillary thyroid carcinomas (PTCs) is prone to significant observer variation due to different thresholds of RAS-like nuclear changes among pathologists. This gap recently widened due to a defensive attitude by Western pathologists where malpractice litigation is significant. Cases with [...] Read more.
Histopathological diagnosis of papillary thyroid carcinomas (PTCs) is prone to significant observer variation due to different thresholds of RAS-like nuclear changes among pathologists. This gap recently widened due to a defensive attitude by Western pathologists where malpractice litigation is significant. Cases with delicate RAS-like nuclear changes are follicular adenomas when they are noninvasive, follicular carcinomas when invasive, and follicular variant PTCs when they have fully developed PTC-type nuclear features in Asian practice. The different diagnostic threshold of PTC nuclear features resulted in a high (50–90%) incidence of BRAFV600E mutation of PTCs in most Asian countries, whereas it was low (35–50%) in most Western patient cohorts. The contamination of indolent RAS-like tumors in the malignant PTC category in Western patient cohorts explains why the BRAFV600E gene test identifies aggressive PTCs. However, the BRAFV600E test has no prognostic value for Asian PTC patients because most biologically benign or low-risk RAS-like tumors are excluded from PTC. All prognostic analyses of thyroid carcinomas before 2017 must be re-evaluated because most clinical guidelines were established based on data obtained from Western patient cohorts where a significant number of indolent RAS-like tumors were misclassified in the malignant category. Full article
(This article belongs to the Special Issue Molecular Advances and Targeted Therapy in Asian Thyroid Practice)
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