scholarly journals Effect of Valproic Acid on miRNAs Affecting Histone Deacetylase in a Model of Anaplastic Thyroid Cancer

2021 ◽  
Author(s):  
Nur Selvi Günel ◽  
Nihal Birden ◽  
Cansu Çalışkan Kurt ◽  
Bakiye Göker Bağca ◽  
behrouz shademan ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Expression Patterns ◽  
Endocrine System ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Rt Pcr ◽  
Surgical Interventions ◽  
Genes Expression

Abstract Thyroid cancer is the most common malignant tumor of the endocrine system seen in the thyroid gland. More than 90% of thyroid cancers comprise papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although anaplastic thyroid carcinoma (ATC) accounts for less than 2% of thyroid cancer. But patients' lifespan after diagnosis is about 6 months. Surgical interventions, radioactive iodine use, and chemotherapy are not sufficient in the treatment of ATC, so alternative therapies are needed. The WST-1 assay test was performed to evaluate the anti-proliferative effects of Valproic acid (VPA). Also, Effect of VPA on miRNAs affecting histone deacetylase were determined by Quantitative RT-PCR. In BRAFV600E / mut SW1736 (SW1736) cell line IC50 dose for VPA found 1.6 mg/ml. in our study, the level of oncogenic genes expression in cells treated with VPA, including miR-184, miR-222-5p, miR-124-3p, and miR-328-3p, decreased. Also, the expression of tumor inhibitory genes is miR-323-5p, miR-182-5p, miR-138-5p, miR-217, miR-15a-5p, miR-29b-3p, miR-324-5p and miR-101- 5p increased significantly. VPA can ad-just countless gene expression patterns, including microRNAs (miRNAs), by targeting histone deacetylase (HDAC). We got very promising results with VPA.

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.

scholarly journals Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Graziella Catalano ◽  
Mariateresa Pugliese ◽  
Marco Gallo ◽  
Enrico Brignardello ◽  
Paola Milla ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Overall Survival ◽  
Thyroid Cancer ◽  
Disease Progression ◽  
Histone Deacetylase ◽  
Median Survival ◽  
Histone Deacetylase Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Randomized Controlled ◽  
Deacetylase Inhibitor

Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxelin vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly) and valproic acid (1,000 mg/day); the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered withEudraCT 2008-005221-11.

scholarly journals Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer

2021 ◽  
Author(s):  
Nur Selvi Gunel ◽  
Nihal Birden ◽  
Cansu Caliskan Kurt ◽  
Bakiye Goker Bagca ◽  
Behrouz Shademan ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Anaplastic Thyroid Cancer

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 The novel histone deacetylase inhibitor thailandepsin A inhibits anaplastic thyroid cancer growth

2014 ◽  
Vol 190 (1) ◽  
pp. 191-197 ◽  
Author(s):  
Eric Weinlander ◽  
Yash Somnay ◽  
April D. Harrison ◽  
Cheng Wang ◽  
Yi-Qiang Cheng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Cancer Growth ◽  
The Novel ◽  
Deacetylase Inhibitor

scholarly journals Histone Deacetylase Inhibition Modulates E-Cadherin Expression and Suppresses Migration and Invasion of Anaplastic Thyroid Cancer Cells

2012 ◽  
Vol 97 (7) ◽  
pp. E1150-E1159 ◽  
Author(s):  
Maria Graziella Catalano ◽  
Nicoletta Fortunati ◽  
Mariateresa Pugliese ◽  
Francesca Marano ◽  
Loredana Ortoleva ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Anaplastic Thyroid Cancer ◽  
Migration And Invasion ◽  
Histone Deacetylase Inhibition ◽  
Thyroid Cancer Cells ◽  
E Cadherin

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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