scholarly journals Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Federica Baldan ◽  
Catia Mio ◽  
Lorenzo Allegri ◽  
Cinzia Puppin ◽  
Diego Russo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Line ◽  
Parp Inhibitor ◽  
Hdac Inhibitors ◽  
Anaplastic Thyroid Cancer ◽  
Parp Inhibitors ◽  
Anaplastic Thyroid Carcinoma ◽  
Specific Gene ◽  
Mrna Levels ◽  
Wide Range

Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the possible synergy between the two types of compounds has been investigated. The ATC-derived cell line SW1736 has been treated with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the PARP inhibitor PJ34, alone or in combination. In terms of cell viability, the combination index value was always lower than 1 at various tested dosages, indicating, therefore, synergy in a wide range of doses for both compounds. Synergy was also observed in induction of apoptosis. In terms of thyroid-specific gene expression, synergy was observed for TSHR mRNA levels but not for NIS, TTF1, TTF2, and PAX8 mRNA levels. Altogether, these data suggest that the combined use of HDAC and PARP inhibitors may be a useful strategy for treatment of ATC.

scholarly journals Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells

2006 ◽  
Vol 191 (2) ◽  
pp. 465-472 ◽  
Author(s):  
Maria G Catalano ◽  
Nicoletta Fortunati ◽  
Mariateresa Pugliese ◽  
Roberta Poli ◽  
Ornella Bosco ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Topoisomerase Ii ◽  
Human Cancer ◽  
Combined Therapy ◽  
Survival Rates ◽  
Hdac Inhibitors ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma

Multimodality treatments (i.e. surgery, chemotherapy, and radiotherapy) are recommended for anaplastic thyroid carcinoma (ATC), an extremely lethal human cancer, but to date there is little evidence that such approaches improve survival rates. It is thus necessary to seek new therapeutic tools. Histone deacetylase (HDAC) inhibitors are a promising class of anti-neoplastic agents that induce differentiation and apoptosis. Moreover, they may enhance the cytotoxicity of drugs targeting DNA through acetylation of histones. Using two ATC cell lines (CAL-62 and ARO), we show here that valproic acid (VPA), a clinically available HDAC inhibitor, enhances the activity of doxorubicin, whose anti-tumor properties involve binding to DNA and inhibiting topoisomerase II. A meager 0.7 mM VPA, which corresponds to serum concentrations in patients treated for epilepsy, is able to increase the cytotoxicity of doxorubicin about threefold in CAL-62 cells and twofold in ARO cells. The sensitizing effect, which is through histone acetylation, involves increased apoptosis, which is also shown by the increased caspase 3 activation and the enhancement of doxorubicin-induced G2 cell cycle arrest. These results might offer a rationale for clinical studies of a new combined therapy in an effort to improve the outcome of patients with anaplastic thyroid cancer.

Effects of melatonin on the toxicity and proliferation of human anaplastic thyroid cancer cell line

2021 ◽  
Vol 123 (3) ◽  
pp. 151700
Author(s):  
Marjan Ghorbani-Anarkooli ◽  
Sara Dabirian ◽  
Adib Zendedel ◽  
Hasan Moladoust ◽  
Mohammad hadi Bahadori
Keyword(s):  
Thyroid Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Line

scholarly journals Thyroid Carcinoma with Pituitary Metastases: 2 Case Reports and Literature Review

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Weiying Lim ◽  
Dawn Shaoting Lim ◽  
Chiaw Ling Chng ◽  
Adoree Yiying Lim
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Radioiodine Therapy ◽  
Follicular Thyroid Carcinoma ◽  
Case Reports ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Pituitary Metastases ◽  
History Of ◽  
Loss Of Appetite

We present 2 patients with pituitary metastases from thyroid carcinoma—the first from anaplastic thyroid carcinoma and the second from follicular thyroid carcinoma. The first patient, a 50-year-old lady, presented with 2-week history of hoarseness of voice, dysphagia, dyspnoea, and neck swelling. Imaging revealed metastatic thyroid cancer to lymph nodes and bone. Histology from surgery confirmed anaplastic thyroid cancer. She was found to have pituitary metastases postoperatively when she presented with nonvertiginous dizziness. She subsequently underwent radiotherapy and radioiodine treatment but passed away from complications. The second patient, a 65-year-old lady, presented with loss of appetite and weight with increased goitre size and dyspnoea. Surgery was performed in view of compressive symptoms and histology confirmed follicular thyroid carcinoma. Imaging revealed metastases to bone, lung, and pituitary. She also had panhypopituitarism with hyperprolactinemia and diabetes insipidus. She received radioiodine therapy but eventually passed away from complications.

scholarly journals HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line

2020 ◽  
Vol 26 (4) ◽  
pp. 2523-2535
Author(s):  
Luca Hegedűs ◽  
Dominika Rittler ◽  
Tamás Garay ◽  
Paul Stockhammer ◽  
Ildikó Kovács ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Cancer Cell ◽  
Hdac Inhibition ◽  
Thyroid Cancer Cell Line

scholarly journals Production of multiple cytokines and induction of cachexia in athymic nude mice by a new anaplastic thyroid carcinoma cell line

2003 ◽  
Vol 179 (3) ◽  
pp. 387-394 ◽  
Author(s):  
JW Chang ◽  
KY Yeh ◽  
YC Shen ◽  
JJ Hsieh ◽  
CK Chuang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Cell Line ◽  
Cancer Cell ◽  
Nude Mice ◽  
Cancer Cell Line ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Cancer Cell ◽  
Athymic Nude Mice ◽  
Thyroid Cancer Cell Line

An anaplastic thyroid cancer cell line, Thena, was recently established in our laboratory following radical thyroidectomy of a patient with anaplastic thyroid cancer. Microscopically, Thena cells were spindle-shaped or small round cells. Thena cells were reactive with cytokeratin AE1/AE3 antibodies, epithelial membrane antigen, interleukin (IL)-6, epithelial growth factor receptor, transforming growth factor (TGF)-alpha, vascular endothelial growth factor, and vimentin. Thena cells secreted high levels of IL-6, leukemia inhibitor factor (LIF), tumor necrosis factor (TNF)-alpha, and TGF-beta1 in the culture supernatants, as determined by enzyme-linked immunosorbent assay. When subcutaneously injected with Thena cells, athymic nude mice developed tumor masses in the skin within 2 weeks. Furthermore, Thena cells induced cachexia in these tumor-bearing mice. High levels of human IL-6, LIF and TGF-beta1 were detected in the mouse sera. To our knowledge, the Thena cell line is the first thyroid cancer cell line reported to induce cachexia in nude mice. This cachectic animal model is worthy of further study to explore the treatment of thyroid cancer-induced cachexia.

scholarly journals CLM3, a Multitarget Tyrosine Kinase Inhibitor With Antiangiogenic Properties, Is Active Against Primary Anaplastic Thyroid Cancer In Vitro and In Vivo

2014 ◽  
Vol 99 (4) ◽  
pp. E572-E581 ◽  
Author(s):  
Alessandro Antonelli ◽  
Guido Bocci ◽  
Poupak Fallahi ◽  
Concettina La Motta ◽  
Silvia Martina Ferrari ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Thyroid Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Cell Line ◽  
Growth Factor Receptor ◽  
Anaplastic Thyroid Cancer ◽  
Antiangiogenic Activity ◽  
Epidermal Growth

Context and Objective: We have studied the antitumor activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) proposed for a multiple signal transduction inhibition [including the RET tyrosine kinase, epidermal growth factor receptor, and vascular endothelial growth factor (VEGF) receptor and with antiangiogenic activity] in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer), and in an ATC-cell line (AF). Design and Main Outcome Measures: CLM3 was tested in primary ATC cells at the concentrations of 5, 10, 30, and 50 μM; in 8305C cells, in AF cells, at 1, 5, 10, 30, 50, or 100 μM; and in AF cells in CD nu/nu mice. Results: CLM3 significantly inhibited the proliferation of 8305C and AF cells, also inducing apoptosis. A significant reduction of proliferation with CLM3 in ATC cells (P < .01, ANOVA) was shown. CLM3 increased the percentage of apoptotic ATC cells dose dependently (P < .001, ANOVA) and inhibited migration (P < .01) and invasion (P < .001). The AF cell line was injected sc in CD nu/nu mice, and tumor masses became detectable 15 days later. CLM3 (50 mg/kg per die) significantly inhibited tumor growth (starting 16 d after the beginning of treatment). CLM3 significantly decreased the VEGF-A expression and microvessel density in AF tumor tissues. Furthermore, CLM3 inhibited epidermal growth factor receptor, AKT, and ERK1/2 phosphorylation and down-regulated cyclin D1 in 8305C and AF cells. Conclusions: The antitumor and antiangiogenic activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) is very promising in anaplastic thyroid cancer, opening the way to a future clinical evaluation.

scholarly journals Recent advances and emerging therapies in anaplastic thyroid carcinoma

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 87 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Mark Zafereo ◽  
Michelle D. Williams ◽  
Renata Ferrarotto ◽  
Ramona Dadu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Thyroid Cancer ◽  
Poor Prognosis ◽  
Recent Progress ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Novel Therapies ◽  
Emerging Therapies ◽  
Improved Outcomes

Anaplastic thyroid cancer is a rare and aggressive thyroid cancer with an overall survival measured in months. Because of this poor prognosis and often advanced age at presentation, these patients have traditionally been treated palliatively and referred for hospice. However, recent progress using novel therapies has energized the field, and several promising clinical trials are now available for these patients. This review will highlight this progress and the potential treatments that could pave the way to improved outcomes and quality of life for patients with this disease.

scholarly journals Novel role of ASH1L histone methyltransferase in anaplastic thyroid carcinoma

2020 ◽  
Vol 295 (26) ◽  
pp. 8834-8845 ◽  
Author(s):  
Bin Xu ◽  
Tingting Qin ◽  
Jingcheng Yu ◽  
Thomas J. Giordano ◽  
Maureen A. Sartor ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Anaplastic Thyroid Cancer ◽  
Histone Methyltransferase ◽  
Anaplastic Thyroid Carcinoma ◽  
Average Life Expectancy ◽  
Upstream Regulator ◽  
Histone Lysine Methyltransferase ◽  
Lysine Methyltransferase

Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, with an average life expectancy of ∼6 months from the time of diagnosis. The genetic and epigenetic changes that underlie this malignancy are incompletely understood. We found that ASH1-like histone lysine methyltransferase (ASH1L) is overexpressed in ATC relative to the much less aggressive and more common differentiated thyroid cancer. This increased expression was due at least in part to reduced levels of microRNA-200b-3p (miR-200b-3p), which represses ASH1L expression, in ATC. Genetic knockout of ASH1L protein expression in ATC cell lines decreased cell growth both in culture and in mouse xenografts. RNA-Seq analysis of ASH1L knockout versus WT ATC cell lines revealed that ASH1L is involved in the regulation of numerous cancer-related genes and gene sets. The pro-oncogenic long noncoding RNA colon cancer-associated transcript 1 (CCAT1) was one of the most highly (approximately 68-fold) down-regulated transcripts in ASH1L knockout cells. Therefore, we investigated CCAT1 as a potential mediator of the growth-inducing activity of ASH1L. Supporting this hypothesis, CCAT1 knockdown in ATC cells decreased their growth rate, and ChIP-Seq data indicated that CCAT1 is likely a direct target of ASH1L's histone methyltransferase activity. These results indicate that ASH1L contributes to the aggressiveness of ATC and suggest that ASH1L, along with its upstream regulator miR-200b-3p and its downstream mediator CCAT1, represents a potential therapeutic target in ATC.

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