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Anaplastic thyroid cancer

Ling Ma, Qiao Cheng
Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid malignancies and resistant to chemotherapy. Little is known on the underlying mechanisms of ATC resistance to chemotherapy. In our work, we identified that 6-phosphogluconate dehydrogenase (6PGD) is critically involved in the development of ATC resistance to doxorubicin. We found that 6PGD mRNA, protein and enzyme activity levels are significantly upregulated in ATC cells during the prolonged exposure to doxorubicin in a time-dependent manner...
March 10, 2018: Biochemical and Biophysical Research Communications
Chien-Liang Liu, Po-Sheng Yang, Ming-Nan Chien, Yuan-Ching Chang, Chi-Hsin Lin, Shih-Ping Cheng
SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61-68% of papillary thyroid cancer and 41-50% of follicular thyroid cancer...
March 12, 2018: Histochemistry and Cell Biology
Zhen-Wei Zou, Ting Liu, Yong Li, Peng Chen, Xin Peng, Charlie Ma, Wen-Jie Zhang, Pin-Dong Li
Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo...
March 1, 2018: Redox Biology
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Ilaria Ruffilli, Giusy Elia, Francesca Ragusa, Anna Fioravanti, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC‑cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 µM) was tested by WST‑1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice...
March 8, 2018: Oncology Reports
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Giusy Elia, Ilaria Ruffilli, Francesca Ragusa, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages...
March 8, 2018: Oncology Reports
Ankit A Shah, Preeti P Jain, Anjaney S Dubey, Ghanish N Panjwani, Hiral A Shah
Context: To share clinicopathological data of thyroid carcinoma from a high volume Tertiary Care Centre in East India. Aim: To share the epidemiology and clinicopathological presentation of thyroid cancer at a high volume Tertiary Care Center in East India. Settings and Design: Retrospective observational study. Subjects and Methods: Forty-two consecutive patients of thyroid neoplasm diagnosed by fine needle aspiration cytology (FNAC) and primarily underwent surgical treatment from July 2005 to June 2012 were included...
January 2018: Journal of Cancer Research and Therapeutics
Sibel Azizenur Ozturk, Ebru Alp, Atiye Seda Yar Saglam, Ece Konac, Emine Sevda Menevse
Context: Thyroid cancers (TCs) are the most common endocrine malignancies. There were two problems with the current cancer chemotherapy: the ineffectiveness of treatment due to resistance to cancer cell, and the toxic effect on normal cells. Aims: This study was aimed to determine the effects of thymoquinone (TQ) and genistein (Gen) phytotherapeutics on telomerase activity, angiogenesis, and apoptosis in follicular and anaplastic thyroid cancer cells (TCCs). Materials and Methods: Cell viability, caspase-3 (CASP-3) activity, and messenger RNA (mRNA) expression levels of human telomerase reverse transcriptase (hTERT), phosphatase and tensin homolog (PTEN), nuclear factor-kappa B (NF-kB), cyclin-dependent kinase inhibitor 1 (p21), and vascular endothelial growth factor-A (VEGF-A) genes were analyzed...
January 2018: Journal of Cancer Research and Therapeutics
Birthe Heitkötter, Konrad Steinestel, Marcel Trautmann, Inga Grünewald, Peter Barth, Heidrun Gevensleben, Martin Bögemann, Eva Wardelmann, Wolfgang Hartmann, Kambiz Rahbar, Sebastian Huss
Aim: PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions. Methods: Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining...
February 9, 2018: Oncotarget
P W Shield, S J Crouch, D J Papadimos, M D Walsh
INTRODUCTION: We evaluated immunohistochemical staining for thyroid peroxidase (TPO), a glycoprotein found in the apical plasma membrane of thyroid follicular cells, as a marker for metastatic PTC in FNA samples and compared results with thyroglobulin (Tg) and thyroid transcription factor 1 (TTF1) staining. METHODS: Cell block sections prepared from 100 FNA specimens were stained with a rabbit monoclonal antibody to TPO (EP159). The FNAs included 64 metastatic malignancies from non-thyroid primary sites, including 18 lung, and 36 cases of thyroid tumours (29 PTC, six cases of medullary thyroid carcinoma and one thyroid anaplastic carcinoma)...
March 6, 2018: Cytopathology: Official Journal of the British Society for Clinical Cytology
Chih-Yuan Wang, Hao-Ai Shui, Tien-Chun Chang
This study tested the hypothesis that the effects of lovastatin on anaplastic thyroid cancer cell growth are mediated by upregulation of transketolase (TKT) expression. The effects of lovastatin on TKT protein levels in ARO cells were determined using western blot and proteomic analyses. After treatment with lovastatin and oxythiamine, the in vitro and in vivo growth of ARO cells was determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assays and tumor xenografts in nude mice...
March 2, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Francesca Galdiero, Anna Maria Bello, Anna Spina, Anna Capiluongo, Sophie Liuu, Margot De Marco, Alessandra Rosati, Mario Capunzo, Maria Napolitano, Emilia Vuttariello, Mario Monaco, Daniela Califano, Maria Caterina Turco, Gennaro Chiappetta, Joëlle Vinh, Giovanni Chiappetta
BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies...
January 30, 2018: Oncotarget
Thomas C Beadnell, Kelsey W Nassar, Madison M Rose, Erin G Clark, Brian P Danysh, Marie-Claude Hofmann, Nikita Pozdeyev, Rebecca E Schweppe
Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway...
February 28, 2018: Oncogenesis
Naris Nilubol, ZiQiang Yuan, Giulio F Paciotti, Lawrence Tamarkin, Carmen Sanchez, Kelli Gaskins, Esther M Freedman, Shugeng Cao, Jielu Zhao, David G I Kingston, Steven K Libutti, Electron Kebebew
Background: The advantages of nanomedicines include preferential delivery of the payload directly to tumor tissues. CYT-21625 is the novel, first-in-class gold nanomedicine designed to target tumor vasculature and cancer cells by specifically delivering recombinant human tumor necrosis factor alpha (rhTNF) and a paclitaxel prodrug. Methods: We analyzed TNF receptor expression in publicly available gene expression profiling data and in thyroid tissue samples. Mice with metastatic FTC-133 and 8505C xenografts and the MEN1 conditional knock-out mice were treated weekly with CYT-21625 and gold nanoparticles with rhTNF only (CYT-6091); controls included mice treated with either paclitaxel or saline...
February 22, 2018: Journal of the National Cancer Institute
Ji Min Oh, Senthilkumar Kalimuthu, Prakash Gangadaran, Se Hwan Baek, Liya Zhu, Ho Won Lee, Ramya Lakshmi Rajendran, Chae Moon Hong, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Radioactive-iodine (RAI) therapy is typically unprevailing as anaplastic thyroid cancer (ATC) management, owing to the decrease in the endogenous sodium iodide symporter (NIS) expression. Therefore, new strategies for NIS re-induction are required to improve the efficacy of RAI therapy in ATC. In this study, we developed a novel high-throughput NIS enhancer screening platform using a dual reporter gene system to identify a potent tyrosine kinase inhibitor (TKI) and selected a new hit compound, K905-0266 TKI...
January 23, 2018: Oncotarget
Emira Ayroldi, Maria Grazia Petrillo, Maria Cristina Marchetti, Lorenza Cannarile, Simona Ronchetti, Erika Ricci, Luigi Cari, Nicola Avenia, Sonia Moretti, Efisio Puxeddu, Carlo Riccardi
Long glucocorticoid-induced leucine zipper (L-GILZ) has recently been implicated in cancer cell proliferation. Here, we investigated its role in human thyroid cancer cells. L-GILZ protein was highly expressed in well-differentiated cancer cells from thyroid cancer patients and differentiated thyroid cancer cell lines, but poorly expressed in anaplastic tumors. A fusion protein containing L-GILZ, when overexpressed in an L-GILZ-deficient 8505C cell line derived from undifferentiated human thyroid cancer tissue, inhibited cellular proliferation in vitro...
February 21, 2018: Cell Death & Disease
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
Qiang Chen, Qing Huang, Jia-Xin Yan, Chao Li, Jin-Yi Lang
RATIONALE: Primary undifferentiated pleomorphic sarcoma is extremely rare in the thyroid, and can be easily misdiagnosed as anaplastic thyroid cancer. PATIENT CONCERNS: We present a case of a 71-year-old woman who presented with a rapidly growing painless mass in the neck. DIAGNOSES-INTERVENTIONS-OUTCOMES: Computed tomography showed a large hypointense mass with hyperdense areas involving whole of the right lobe of thyroid gland and fine-needle aspiration cytology found a few atypical cells...
February 2018: Medicine (Baltimore)
Ewelina Motylewska, Tomasz Stępień, Magdalena Borkowska, Krzysztof Kuzdak, Agnieszka Siejka, Jan Komorowski, Henryk Stępień, Hanna Ławnicka
INTRODUCTION: βKlotho (βKL) is known to act as co-receptor for fibroblast growth factor receptor 4 (FGFR4) which is the main cognate receptor for fibroblast growth factor 19 (FGF19). Dysregulation of this FGF19/FGFR4/βKL signaling axis has been implicated in the pathogenesis of several cancers. However, its role in the pathogenesis of thyroid cancer has not been determined. MATERIALS AND METHODS: The aim of this study was to assess FGF19, FGFR4 and βKL concentrations in a group of 36 patients with papillary thyroid cancer (PTC), 11 patients with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and a group of 19 subjects with multinodular nontoxic goiter (MNG)...
February 10, 2018: Cytokine
Alessia Parascandolo, Mikko O Laukkanen, Nancy De Rosa, Clara Ugolini, Maria Carmela Cantisani, Anna Maria Cirafici, Fulvio Basolo, Massimo Santoro, Maria Domenica Castellone
Sonic Hedgehog (Shh) pathway regulates embryonic development of different organs including the thyroid gland. The aberrant activation of Shh signaling has been found in several types of cancer and according to recent evidences it represents an important regulator of tumor-stroma interaction. In this study, we have analyzed expression, activation and molecular mechanisms regulating the Shh pathway and its involvement in the modulation of tumor stroma interaction in anaplastic thyroid cancer (ATC) cells. Our results suggest that Shh signaling undergoes a dual mechanism of induction in ATC cells: 1) a basal non-canonical Smo-dependent activation of Gli transcription factor that is partly caused by interaction with the RAS/BRAF/MEK oncogenic pathway and is characterized by the absence of Shh ligand expression in thyroid cancer cells and 2) a paracrine response of cancer cells to Shh ligand secreted by tumor stroma (fibroblasts and mesenchymal stromal cells, MSCs) inducing cancer cell migration and in vitro tumorigenesis...
January 12, 2018: Oncotarget
Dumitru A Iacobas, Neha Y Tuli, Sanda Iacobas, John K Rasamny, Augustine Moscatello, Jan Geliebter, Raj K Tiwari
We hypothesize that distinct cell phenotypes are governed by different sets of gene master regulators (GMRs) whose strongly protected (by the homeostatic mechanisms) abundance modulates most cell processes by coordinating the expression of numerous genes from the corresponding functional pathways. Gene Commanding Height (GCH), a composite measure of gene expression control and coordination, is introduced to establish the gene hierarchy in each phenotype. If the hypothesis is true, than one can selectively destroy cancer nodules from a heterogeneous tissue by altering the expression of genes whose GCHs are high in cancer but low in normal cell phenotype...
January 5, 2018: Oncotarget
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