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molecular thyroid cancer

Muhammad Khairi Ahmad, Nur Ainina Abdollah, Nurul Husna Shafie, Narazah Mohd Yusof, Siti Razila Abdul Razak
Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells...
February 2018: Cancer Biology & Medicine
Giulio Innamorati, Thomas M Wilkie, Havish S Kantheti, Maria Teresa Valenti, Luca Dalle Carbonare, Luca Giacomello, Marco Parenti, Davide Melisi, Claudio Bassi
BACKGROUND: Mutations activating the α subunit of heterotrimeric Gs protein are associated with a number of highly specific pathological molecular phenotypes. One of the best characterized is the McCune Albright syndrome. The disease presents with an increased incidence of neoplasias in specific tissues. MAIN BODY: A similar repertoire of neoplasms can develop whether mutations occur spontaneously in somatic tissues during fetal development or after birth. Glands are the most "permissive" tissues, recently found to include the entire gastrointestinal tract...
March 15, 2018: BMC Cancer
Geneviève Dom, Sandra Frank, Sebastien Floor, Pashalina Kehagias, Frederick Libert, Catherine Hoang, Guy Andry, Alex Spinette, Ligia Craciun, Nicolas de Saint Aubin, Christophe Tresallet, Frederique Tissier, Frederique Savagner, Samira Majjaj, Ilse Gutierrez-Roelens, Etienne Marbaix, Jacques E Dumont, Carine Maenhaut
Non-autonomous thyroid nodules are common in the general population with a proportion found to be cancerous. A current challenge in the field is to be able to distinguish benign adenoma (FA) from preoperatively malignant thyroid follicular carcinoma (FTC), which are very similar both histologically and genetically. One controversial issue, which is currently not understood, is whether both tumor types represent different molecular entities or rather a biological continuum. To gain a better insight into FA and FTC tumorigenesis, we defined their molecular profiles by mRNA and miRNA microarray...
February 13, 2018: Oncotarget
Xin Chen, Mingzhe Li, Hongwei Zhou, Li Zhang
MicroRNA-132 (miR-132) has been proven to be a tumor suppressor in several types of tumors. However, the expression andthe role of miR-132 in human thyroid cancer are still poorly understood. The aim of the present study was to examine the potential roles and molecular mechanism of miR-132 in thyroid cancer. We found that miR-132 expression levels were significantly downregulated in thyroid cancer tissues and cell lines. Function assays showed that overexpression of miR-132 in TPC1 inhibited cell proliferation, migration and invasion...
March 9, 2018: Oncology Research
Li-Ou Han, Xin-Yu Li, Ming-Ming Cao, Yan Cao, Li-Hong Zhou
New molecular signatures are needed to improve the diagnosis of thyroid cancer (TC) and avoid unnecessary surgeries. In this study, we aimed to develop a robust and individualized diagnostic signature in TC. Gene expression profiles of tumor and nontumor samples were from 13 microarray datasets of Gene Expression Omnibus (GEO) database and one RNA-sequencing dataset of The Cancer Genome Atlas (TCGA). A total of 1246 samples were divided into a training set (N = 435), a test set (N = 247), and one independent validation set (N = 564)...
March 9, 2018: Cancer Medicine
W Liang, F Sun
OBJECTIVE: To identify novel clinically relevant genes in papillary thyroid carcinoma from public databases. METHODS: Four original microarray datasets, GSE3678, GSE3467, GSE33630 and GSE58545, were downloaded. Differentially expressed genes (DEGs) were filtered from integrated data. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction...
March 8, 2018: Journal of Endocrinological Investigation
Trevor E Angell, Chirag M Vyas, Justine A Barletta, Edmund S Cibas, Nancy L Cho, Gerard M Doherty, Atul A Gawande, Brooke E Howitt, Jeffrey F Krane, Ellen Marqusee, Kyle C Strickland, Erik K Alexander, Francis D Moore, Matthew A Nehs
BACKGROUND: Diagnostic hemithyroidectomy (HT) is the most widely recommended surgical procedure for a nodule with indeterminate cytology; however, additional details may make initial total thyroidectomy (TT) preferable. We sought to identify patient-specific factors (PSFs) associated with initial TT in patients with indeterminate thyroid nodules. METHODS: Retrospective analysis of all patients with a thyroid nodule ≥ 1 cm and initial cytology of atypia of undetermined significance or suspicious for follicular neoplasm between 2012 and 2015 who underwent thyroidectomy...
March 8, 2018: Annals of Surgical Oncology
V Petrosino, G Motta, G Tenore, M Coletta, A Guariglia, D Testa
Previous literature has highlighted the mechanisms of molecular toxicity induced by substances such as arsenic, cadmium, chromium, nickel, lead, barium and PCBs. The research was carried out on 20 volunteers, all the patients gave their consent to the research: the aim of the study was to evaluate the presence of metals and PCBs in these different matrices (blood and hair), correlating the biochemical data to pathological conditions present, and also to the area in which patients resided. Various quantitative determinations were carried out on samples of blood and hair for 14 heavy metals and on blood samples for 12 PCBs...
March 8, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Sann Y Mon, Gregory Riedlinger, Collette E Abbott, Raja Seethala, N Paul Ohori, Marina N Nikiforova, Yuri E Nikiforov, Steven P Hodak
BACKGROUND: Thyroid-stimulating hormone receptor (TSHR) gene mutations play a critical role in thyroid cell proliferation and function. They are found in 20%-82% of hyperfunctioning nodules, hyperfunctioning follicular thyroid cancers (FTC), and papillary thyroid cancers (PTC). The diagnostic importance of TSHR mutation testing in fine needle aspiration (FNA) specimens remains unstudied. METHODS: To examine the association of TSHR mutations with the functional status and surgical outcomes of thyroid nodules, we evaluated 703 consecutive thyroid FNA samples with indeterminate cytology for TSHR mutations using next-generation sequencing...
March 8, 2018: Diagnostic Cytopathology
Marlena Godlewska, Wanda Krasuska, Barbara Czarnocka
Thyroid peroxidase (TPO) is an enzyme and autoantigen expressed in thyroid and breast tissues. Thyroid TPO undergoes a complex maturation process however, nothing is known about post-translational modifications of breast-expressed TPO. In this study, we have investigated the biochemical properties of TPO expressed in normal and cancerous human breast tissues, and the maturation process and antigenicity of TPO present in a panel of human breast tissue-derived cell lines. We found that the molecular weight of breast TPO was slightly lower than that of thyroid TPO due to decreased glycosylation and as suggest results of Western blot also shorter amino acid chain...
2018: PloS One
Xiaomeng Li, Xianhui Ruan, Peitao Zhang, Yang Yu, Ming Gao, Shukai Yuan, Zewei Zhao, Jie Yang, Li Zhao
The T-box transcription factor TBX3 has been implicated in the patterning and differentiation of a number of tissues during embryonic development, and is overexpressed in a variety of cancers; however, the precise function of TBX3 in papillary thyroid carcinoma (PTC) development remains to be determined. In the current study, we report downregulation of TBX3 in PTC cells delays the G1/S-phase transition, decreases cell growth in vitro, and inhibits tumor formation in vivo. We identified p57KIP2 as a novel downstream target that serves as the key mediator of TBX3's control over PTC cell proliferation...
March 7, 2018: Oncogene
Cosimo Durante, Giorgio Grani, Livia Lamartina, Sebastiano Filetti, Susan J Mandel, David S Cooper
Importance: Thyroid nodules are common, being detected in up to 65% of the general population. This is likely due to the increased use of diagnostic imaging for purposes unrelated to the thyroid. Most thyroid nodules are benign, clinically insignificant, and safely managed with a surveillance program. The main goal of initial and long-term follow-up is identification of the small subgroup of nodules that harbor a clinically significant cancer (≈10%), cause compressive symptoms (≈5%), or progress to functional disease (≈5%)...
March 6, 2018: JAMA: the Journal of the American Medical Association
Raúl F Pérez, Juan Ramón Tejedor, Gustavo F Bayón, Agustín F Fernández, Mario F Fraga
Cancer is an aging-associated disease, but the underlying molecular links between these processes are still largely unknown. Gene promoters that become hypermethylated in aging and cancer share a common chromatin signature in ES cells. In addition, there is also global DNA hypomethylation in both processes. However, the similarity of the regions where this loss of DNA methylation occurs is currently not well characterized, and it is unknown if such regions also share a common chromatin signature in aging and cancer...
March 5, 2018: Aging Cell
Mark Lupo, Richard Guttler, Zsofia Geck, Theresa R Tonozzi, Anja Kammesheidt, Glenn D Braunstein
OBJECTIVE: Circulating tumor DNA (ctDNA), a subset of circulating free DNA (cfDNA), measurement is a potential biomarker for thyroid cancer. We determined the performance of a ctDNA panel for detection of thyroid malignancy in patients with thyroid nodules. METHODS: Sixty-six patients with thyroid nodules without a prior history of cancer enrolled in a prospective, one-year study in which blood was drawn for ctDNA analysis prior to undergoing fine-needle aspiration biopsy (FNAB) of thyroid nodules...
March 2, 2018: Endocrine Practice
Lei Zhang, Wen Liu, Qun Wang, Qinpei Li, Huijuan Wang, Jun Wang, Tieshan Teng, Mingliang Chen, Ailing Ji, Yanzhang Li
Medullary thyroid cancer (MTC) is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1) plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) was identified from the Specs compounds database using the protein structure-guided virtual screening approach...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Marta Kotlarek, Anna Kubiak, Małgorzata Czetwertyńska, Michał Świerniak, Wojciech Gierlikowski, Monika Kolanowska, Elwira Bakuła-Zalewska, Sissy M Jhiang, Krystian Jażdżewski, Anna Wójcicka
Aberrant expression of the sodium-iodide symporter (NIS) and the resistance to post-operative radioactive iodide treatment is a crucial cause of higher mortality of some thyroid cancer patients. In this study, we analyzed the impact of miR-146a on the expression and function of NIS and on the overall survival of thyroid cancer patients. The study included 2441 patients (2163 women; 278 men); including 359 cases with follicular variant of papillary thyroid carcinoma (fvPTC). miR: NIS interactions were analyzed in cell lines using in vivo binding and inhibition assays and radioactive iodine uptake assays...
February 26, 2018: International Journal of Molecular Sciences
Zongjuan Li, Xiangdong Xu, Yizhuo Li, Kun Zou, Zhuo Zhang, Xiaoying Xu, Yina Liao, Xinrui Zhao, Wei Jiang, Wendan Yu, Wei Guo, Yiming Chen, Yixin Li, Miao Chen, Wu-Guo Deng, Liren Li, Lijuan Zou
BACKGROUND/AIMS: PI3KCA and mutant p53 are associated with tumorigenesis and the development of cancers. NVP-BKM120, a selective pan-PI3K inhibitor, exerts the antitumor activity by suppressing the PI3K signaling pathway. Prima-1Met, a low molecular weight compound, can rescue the gain-of-function of mutant p53 by restoring its transcriptional function. In this study, we investigated whether PI3K inhibition combined with mutant p53 reactivation could enhance the antitumor effect in thyroid cancer cells...
February 23, 2018: Cellular Physiology and Biochemistry
Marta Kinga Lemieszek, Andrzej Stepulak, Katarzyna Sawa-Wejksza, Arkadiusz Czerwonka, Chrysanthy Ikonomidou, Wojciech Rzeski
Regardless of contemporary improvements in cancer treatment, the results of drug treatment are not always efficacious. Thus, the development of novel approaches that affect cancer cell-specific metabolic pathways are needed. Since much evidence has shown that tumor cell proliferation and motility are stimulated by glutamate via activation of its receptors, use of antagonists to these receptors may be the key to control cancer cell progression. Riluzole noncompetitive metabotropic glutamate receptor 1 (mGluR1) antagonist, commonly used to treat patients with amyotrophic lateral sclerosis (ALS), has shown some antineoplastic properties against melanoma, breast and prostate cancer...
February 28, 2018: Anti-cancer Agents in Medicinal Chemistry
Anna Wojakowska, Laura M Cole, Mykola Chekan, Katarzyna Bednarczyk, Magdalena Maksymiak, Małgorzata Oczko-Wojciechowska, Barbara Jarząb, Malcolm R Clench, Joanna Polańska, Monika Pietrowska, Piotr Widlak
INTRODUCTION: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical man-agement. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies...
2018: Endokrynologia Polska
Lei Cai, Theodoros Michelakos, Teppei Yamada, Song Fan, Xinhui Wang, Joseph H Schwab, Cristina R Ferrone, Soldano Ferrone
Malignant transformation of cells is frequently associated with defective HLA class I antigen processing machinery (APM) component expression. This abnormality may have functional relevance, since it may have a negative impact on tumor cell recognition by cognate T cells. Furthermore, HLA class I APM abnormalities appear to have clinical significance, since they are associated with poor prognosis in several malignant diseases and may play a role in the resistance to immune checkpoint inhibitor-based immunotherapy...
February 27, 2018: Cancer Immunology, Immunotherapy: CII
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