scholarly journals SUN-132 KLF5 Is a Poor Prognostic Marker and Therapeutic Target for Middle Eastern Papillary Thyroid Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Khawla S Al-Kuraya ◽  
Abdul K Siraj ◽  
Pratheeshkumar Poyil ◽  
Divya Padmaja ◽  
Sandeep Kumar Parvathareddy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Critical Role ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Inhibition Of Proliferation ◽  
Over Expression

Abstract Thyroid cancer is the second most common malignancy among females in Saudi Arabia, with Papillary thyroid carcinoma (PTC) accounting for 80-90%. The Kruppel-like factor 5 (Klf5) is a transcription factor that play a critical role in cell transformation, proliferation and oncogenesis. Immunohistochemical analysis of KLF5 was performed in 1219 PTC cases. KLF5 over-expression was noted in 65.1% (793/1219) of PTCs, and was significantly associated with tall-cell variant (p <0.0001), extrathyroidal extension (p = 0.0003), lymph node metastasis (p < 0.0001) and stage IV tumors (p < 0.0001). Significant association was also noted with HIF-1α over-expression (p = 0.0492). Interestingly, KLF5 over-expressing tumors showed poor disease-free survival (p = 0.0066). Functional studies in PTC cell lines showed that KLF5 co-immunoprecipitated with HIF-1α. Knockdown of KLF5 decreased the expression of HIF-1α while KLF5 was not affected by HIF-1α inhibition, suggesting that KLF5 is a functional upstream of HIF-1α. Down-regulation of KLF5 using specific inhibitor, ML264 or siRNA inhibited cell invasion and migration. In addition, treatment of PTC cell lines with ML264 resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Furthermore, silencing of KLF5 significantly decreased the self-renewal ability of spheroids generated from PTC cells. Our findings confer that KLF5 may be a potential therapeutic target for the treatment of papillary thyroid cancer.

scholarly journals Metformin reduces glycometabolism of papillary thyroid carcinoma in vitro and in vivo

2017 ◽  
Vol 58 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Chen-Tian Shen ◽  
Wei-Jun Wei ◽  
Zhong-Ling Qiu ◽  
Hong-Jun Song ◽  
Xin-Yun Zhang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Fdg Uptake ◽  
Dose Dependent

More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0–10 mM for 48 h)-treated cells by 18F-FDG uptake assay and western blotting analysis, respectively. MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo. After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated. 18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro. Xenograft model of PTC using BCPAP cells was achieved successfully. MicroPET/CT imaging showed that in vivo 18F-FDG uptake decreased after treatment with metformin. Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model. In conclusion, metformin could reduce glucose metabolism of PTC in vitro and in vivo. Metformin, by targeting glycometabolism of cancer cells, could be a promising adjuvant therapy alternative in the treatment modality of advanced thyroid carcinoma.

scholarly journals mTOR Pathway Overactivation in BRAF Mutated Papillary Thyroid Carcinoma

2012 ◽  
Vol 97 (7) ◽  
pp. E1139-E1149 ◽  
Author(s):  
Alexandra Faustino ◽  
Joana P. Couto ◽  
Helena Pópulo ◽  
Ana Sofia Rocha ◽  
Fernando Pardal ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Genetic Alterations ◽  
Mtor Pathway ◽  
Expression Vectors ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Pathway Activation

Abstract Context: There are several genetic and molecular evidences suggesting dysregulation of the mammalian target of rapamycin (mTOR) pathway in thyroid neoplasia. Activation of the phosphatidylinositol-3-kinase/AKT pathway by RET/PTC and mutant RAS has already been demonstrated, but no data have been reported for the BRAFV600E mutation. Objective: The aim of this study was to evaluate the activation pattern of the mTOR pathway in malignant thyroid lesions and whether it may be correlated with known genetic alterations, as well as to explore the mechanisms underlying mTOR pathway activation in these neoplasias. Results: We observed, by immunohistochemical evaluation, an up-regulation/activation of the mTOR pathway proteins in thyroid cancer, particularly in conventional papillary thyroid carcinoma (cPTC). Overactivation of the mTOR signaling was particularly evident in cPTC samples harboring the BRAFV600E mutation. Transfection assays with BRAF expression vectors as well as BRAF knockdown by small interfering RNA revealed a positive association between BRAF expression and mTOR pathway activation, which appears to be mediated by pLKB1 Ser428, and emerged as a possible mechanism contributing to the association between BRAF mutation and mTOR pathway up-regulation. When we evaluated the rapamycin in the growth of thyroid cancer cell lines, we detected that cell lines with activating mutations in the MAPK pathway show a higher sensitivity to this drug. Conclusions: We determined that the AKT/mTOR pathway is particularly overactivated in human cPTC harboring the BRAFV600E mutation. Moreover, our results suggest that the mTOR pathway could be a good target to enhance therapy effects in certain types of thyroid carcinoma, namely in those harboring the BRAFV600E mutation.

scholarly journals Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1030 ◽  
Author(s):  
Dumitru A. Iacobas
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Mathematical Object ◽  
Human Thyroid ◽  
Expression Data ◽  
Papillary Thyroid ◽  
Hormone Synthesis ◽  
Thyroid Cancer Cell Lines

Publicly available (own) transcriptomic data have been analyzed to quantify the alteration in functional pathways in thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data have been generated by profiling one case of papillary thyroid carcinoma (PTC) and genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric paradigm that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase in the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that SPINT2 experimental overexpression may force the PTC cells into apoptosis with a negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cell lines before and after lentiviral transfection with DDX19B.

scholarly journals IL13RA2 Is Differentially Regulated in Papillary Thyroid Carcinoma vs Follicular Thyroid Carcinoma

2019 ◽  
Vol 104 (11) ◽  
pp. 5573-5584 ◽  
Author(s):  
Siao Ting Chong ◽  
Khee Ming Tan ◽  
Catherine Y L Kok ◽  
Shou Ping Guan ◽  
Siang Hui Lai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Advanced Tumor

Abstract Context The interleukin-13 receptor alpha2 (IL13RA2), which is known to be overexpressed in glioblastoma multiforme, plays a role in various cellular processes such as cell migration that may contribute to tumor progression. Studies have attributed IL13RA2 to invasion and metastasis in cancers of the ovary, breast, and pancreas, but the pathological role of IL13RA2 in thyroid cancer is still unclear. Objective This study aims to evaluate IL13RA2 expression in thyroid carcinomas and to examine the role of IL13RA2 in the progression of papillary thyroid carcinoma (PTC). Methods IL13RA2 immunochemical staining was performed on tissue microarrays of 137 thyroid carcinomas from patients, and the differential profile of IL13RA2 was validated in thyroid cancer cell lines. In PTC cell lines, we functionally assessed the effects of IL13RA2 underexpression and overexpression on cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT) by using CCK-8, transwell migration assay, quantitative RT-PCR, and Western blot analysis. Results IL13RA2 expression was significantly correlated with advanced tumor T stage (pT3 or pT4; P = 0.001) and regional lymph node metastasis (pN1; P < 0.001). The staining scores of IL13RA2 were significantly higher in PTC compared with follicular subtypes (P < 0.001) and correlated with advanced tumor stage among PTC samples (pT3 or pT4; P = 0.028). Knockdown of IL13RA2 in B-CPAP cells significantly reduced cell viability, cell migration, and EMT markers including N-cadherin, Vimentin, and Snail. Exogenous overexpression of IL13RA2 in K1 cells increased cell migration and EMT, although cell proliferation was not affected. Conclusion IL13RA2 is differentially regulated in PTC and is involved in cell migration by enhancing EMT.

scholarly journals SUN-416 Fatigue and Quality of Life Among Thyroid Cancer Survivors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maki Yukari
Keyword(s):  
Quality Of Life ◽  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cancer Survivors ◽  
Papillary Thyroid ◽  
Explanatory Variables ◽  
Initial Surgery ◽  
Sf 36

Abstract BACKGROUND Fatigue among thyroid cancer survivors is an important issue that needs to be appreciated and managed appropriately. Although several studies have reported potential factors that might be related to postoperative fatigue, the associations have yet to be inconclusive. The purpose of the present study was to estimate the prevalence of clinical fatigue in patients with papillary thyroid carcinoma and to reveal predictive factors, including their quality of life. METHODS A cross-sectional survey was conducted on patients with papillary thyroid carcinoma. Patients who underwent non-curative surgery, or those with recurrent or metastatic PTC, or those with other malignancies were excluded. The primary outcome was fatigue measured by the Cancer Fatigue Scale (CFS), and the secondary outcome was quality of life (QoL) quantified using the SF-36 v2. The following explanatory variables were collected; gender, age, employment status, marital status, co-morbidities, time since initial surgery, types of surgery, replacement of thyroid hormone, use of radioactive iodine, and the level of thyrotropin. The prevalence of clinical fatigue was estimated with the cut-off value of 18/19 of the CFS score. Correlations between the CFS score and the explanatory variables were examined using uni-variable analyses as well as multi-variable analysis. RESULTS Three hundred twenty-one patients participated in the survey. Of them, 258 respondents (80%) were female. The median age was 58 years, and the median time from initial surgery was 6.4 years. The mean and the standard deviation of the CFS score were 17.9 and 9.3, respectively (range: 0-48). The prevalence of clinical fatigue was 42% [95%CI: 36-47%]. Among the variables explored, having a job and scores of the mental component summary, the physical component summary, and the role/social component summary of the SF-36 were inversely associated with the CFS score in both uni- and multivariable analyses. CONCLUSION Postoperative fatigue was common in thyroid cancer survivors. Patients with a job and better QoL, in particular, those with good mental health, maybe at low-risk of developing the burden.

scholarly journals Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

2020 ◽  
Author(s):  
Dumitru A Iacobas
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Mathematical Object ◽  
Human Thyroid ◽  
Expression Data ◽  
Papillary Thyroid ◽  
Hormone Synthesis ◽  
Apoptosis Pathways ◽  
Thyroid Cancer Cell Lines

Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.

Papillary thyroid carcinoma in a 7-year-old boy presenting with a goitre without microcalcifications and enlarged cervical lymph nodes

2021 ◽  
Vol 14 (7) ◽  
pp. e242278
Author(s):  
Maria Cecilia Schultze ◽  
Cintia Castro-Correia ◽  
Maria Bom-Sucesso ◽  
Marianne Becker
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Lung Nodule ◽  
Lymph Node Biopsy ◽  
Papillary Thyroid ◽  
Cervical Lymph Nodes ◽  
Diffuse Infiltration ◽  
Uncommon Presentation ◽  
Metastatic Lung

The most frequent type of thyroid malignancy in children is papillary thyroid carcinoma (PTC), which usually presents as a thyroid nodule, but may also present as a diffuse infiltration with microcalcifications. Herein, we report the case of an uncommon presentation of a PTC in a 7-year-old boy. The child was referred for a goiter with cervical lymphadenopathies. Ultrasonography showed a hypervascularised goiter without microcalcifications but with numerous bilateral cervical nodular formations. A lymph node biopsy revealed metastatic thyroid cancer, hence a total thyroidectomy and complete neck dissection were performed. Histopathology confirmed a PTC. Ablative 131I, 30 mCi was performed 4 months postsurgery. At the end of this treatment, a metastatic lung nodule was identified. Since then, another three ablative 131I treatments have been administered. Thyroid cancers presenting as a diffuse infiltration without microcalcifications are rare. In the presence of lymphadenopathies, thyroid cancer needs to be suspected, even without microcalcifications.

scholarly journals Papillary Thyroid Carcinoma With Cystic Changes in a Patient With Prior History of Toxic Nodule

2020 ◽  
Vol 8 ◽  
pp. 232470962094267
Author(s):  
Gliceida Maria Galarza Fortuna ◽  
Paola Rios ◽  
Ailyn Rivero ◽  
Gabriela Zuniga ◽  
Kathrin Dvir ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Thyroid Nodule ◽  
Thyroid Nodules ◽  
Molecular Testing ◽  
Papillary Thyroid ◽  
Thyroid Lobectomy ◽  
Cystic Changes ◽  
History Of

Thyroid nodules are palpable on up to 7% of asymptomatic patients. Cancer is present in 8% to 16% of those patients with previously identified thyroid nodules. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for approximately 85% of thyroid cancers. Although most appear as solid nodules on ultrasound imaging, a subset of 2.5% to 6% has cystic components. The presence of cystic changes within thyroid nodules decreases the accuracy of fine needle aspiration (FNA) in the diagnosis of thyroid cancer, given the difficulty of obtaining appropriate cellular content. This becomes a diagnostic and therapeutic challenge. We present a case of a 31-year-old female with a 1-month history of palpitations, fatigue, and night sweats, who underwent evaluation, and was diagnosed with subclinical hyperthyroidism. She presented 4 years later with compressive symptoms leading to repeat FNA, showing Bethesda III-atypia of undetermined significance and negative molecular testing. Thyroid lobectomy revealed PTC with cystic changes. This case is a reminder that patients with hyperfunctioning thyroid nodule should have closer follow-up. It poses the diagnostic dilemma of how much is good enough in the evaluation and management of a thyroid nodule. Early detection and action should be the standard of care.

scholarly journals Differential glycolytic profile and Warburg effect in papillary thyroid carcinoma cell lines

2016 ◽  
Vol 36 (6) ◽  
pp. 3673-3681 ◽  
Author(s):  
Raquel Guimarães Coelho ◽  
Juliana De Menezes Cazarin ◽  
João Paulo Albuquerque Cavalcanti De Albuquerque ◽  
Bruno Moulin De Andrade ◽  
Denise P. Carvalho
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Warburg Effect ◽  
Carcinoma Cell ◽  
Papillary Thyroid ◽  
Carcinoma Cell Lines ◽  
Thyroid Carcinoma Cell ◽  
Papillary Thyroid Carcinoma Cell

scholarly journals Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study

2018 ◽  
Vol 19 (10) ◽  
pp. 2948 ◽  
Author(s):  
Paola Caria ◽  
Laura Tronci ◽  
Tinuccia Dettori ◽  
Federica Murgia ◽  
Maria Santoru ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Krebs Cycle ◽  
Metabolic Phenotype ◽  
Gas Chromatography Mass Spectrometry ◽  
Papillary Thyroid ◽  
Time Data ◽  
Krebs Cycle Intermediates ◽  
New Biomarkers

Papillary thyroid carcinoma (PTC), is characterized by a heterogeneous group of cells, including cancer stem cells (CSCs), crucially involved in tumor initiation, progression and recurrence. CSCs appear to have a distinct metabolic phenotype, compared to non-stem cancer cells. How they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. We recently isolated thyrospheres, containing cancer stem-like cells, from B-CPAP and TPC-1 cell lines derived from PTC of the BRAF-like expression profile class, and stem-like cells from Nthy-ori3-1 normal thyreocyte-derived cell line. In the present study, gas chromatography/mass spectrometry metabolomic profiles of cancer thyrospheres were compared to cancer parental adherent cells and to non cancer thyrospheres profiles. A statistically significant decrease of glycolytic pathway metabolites and variations in Krebs cycle metabolites was found in thyrospheres versus parental cells. Moreover, cancer stem-like cells showed statistically significant differences in Krebs cycle intermediates, amino acids, cholesterol, and fatty acids content, compared to non-cancer stem-like cells. For the first time, data are reported on the metabolic profile of PTC cancer stem-like cells and confirm that changes in metabolic pathways can be explored as new biomarkers and targets for therapy in this tumor.

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