Synergistic anticancer activity of sorafenib, paclitaxel, and radiation therapy on anaplastic thyroid cancer in vitro and in vivo

Head & Neck ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 3678-3684
Author(s):  
Soo Young Kim ◽  
Seok‐Mo Kim ◽  
Hojin Chang ◽  
Hang‐Seok Chang ◽  
Cheong Soo Park ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Thyroid Cancer ◽  
Anticancer Activity ◽  
Anaplastic Thyroid Cancer

Efficacy of adavosertib therapy against anaplastic thyroid cancer

2021 ◽  
Author(s):  
Yu-Ling Lu ◽  
Yu-Tung Huang ◽  
Ming-Hsien Wu ◽  
Ting-Chao Chou ◽  
Richard J Wong ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Growth ◽  
Single Agent ◽  
Xenograft Model ◽  
Anaplastic Thyroid Cancer ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Cancer Tumor

Wee1 is a kinase that regulates the G2/M progression by inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease. The therapeutic effects of adavosertib, a Wee1 inhibitor for anaplastic thyroid cancer was evaluated in this study. Adavosertib inhibited cell growth in three anaplastic thyroid cancer cell lines in a dose-dependent manner. Cell cycle analysis revealed cells were accumulated in the G2/M phase. Adavosertib induced caspase-3 activity and led to apoptosis. Adavosertib monotherapy showed significant retardation of the growth of two anaplastic thyroid cancer tumor models. The combination of adavosertib with dabrafenib and trametinib revealed strong synergism in vitro and demonstrated robust suppression of tumor growth in vivo in anaplastic thyroid cancer xenograft models with BRAFV600E mutation. The combination of adavosertib with either sorafenib or lenvatinib also demonstrated synergism in vitro and had strong inhibition of tumor growth in vivo in an anaplastic thyroid cancer xenograft model. No appreciable toxicity appeared in mice treated with either single agent or combination treatment. Our findings suggest adavosertib holds the promise for the treatment of patients with anaplastic thyroid cancer.

scholarly journals Antitumor effects of anlotinib in thyroid cancer

2019 ◽  
Vol 26 (1) ◽  
pp. 153-164 ◽  
Author(s):  
Xianhui Ruan ◽  
Xianle Shi ◽  
Qiman Dong ◽  
Yang Yu ◽  
Xiukun Hou ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Cancer Type ◽  
Papillary Thyroid ◽  
Antitumor Effects ◽  
Effective Therapeutic Strategy

There is no effective treatment for patients with poorly differentiated papillary thyroid cancer or anaplastic thyroid cancer (ATC). Anlotinib, a multi-kinase inhibitor, has already shown antitumor effects in various types of carcinoma in a phase I clinical trial. In this study, we aimed to better understand the effect and efficacy of anlotinib against thyroid carcinoma cells in vitro and in vivo. We found that anlotinib inhibits the cell viability of papillary thyroid cancer and ATC cell lines, likely due to abnormal spindle assembly, G2/M arrest, and activation of TP53 upon anlotinib treatment. Moreover, anlotinib suppresses the migration of thyroid cancer cells in vitro and the growth of xenograft thyroid tumors in mice. Our data demonstrate that anlotinib has significant anticancer activity in thyroid cancer, and potentially offers an effective therapeutic strategy for patients of advanced thyroid cancer type.

scholarly journals Synergistic Anticancer Activity of N-Hydroxy-7-(2-Naphthylthio) Heptanomide, Sorafenib, and Radiation Therapy in Patient-Derived Anaplastic Thyroid Cancer Models

2021 ◽  
Vol 22 (2) ◽  
pp. 536
Author(s):  
Hyeok Jun Yun ◽  
Hee Jun Kim ◽  
Jungmin Kim ◽  
Sang Yong Kim ◽  
Hang-Seok Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Radiation Therapy ◽  
Thyroid Cancer ◽  
Combination Therapy ◽  
Intracellular Signaling ◽  
Xenograft Model ◽  
Anaplastic Thyroid Cancer ◽  
Anticancer Effect ◽  
Mouse Xenograft Model

Anaplastic thyroid cancer (ATC) is an undifferentiated and advanced form of thyroid cancer, accompanied with a high ratio of epigenetic adjustment, which occurs more than genetic mutations. In this study, we aimed to evaluate the synergistic anticancer effect (in vitro and in vivo) of the new combination of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and sorafenib with radiation therapy in pre-clinical models of ATC. The ATC cell lines, YUMC-A1 and YUMC-A2, were isolated from the current patients who were treated with HNHA and sorafenib, either as monotherapy or combination therapy. Synergistic anticancer effect of the combination therapy on the intracellular signaling pathways and cell cycle was assessed via flow cytometry and immunoblot analysis. To examine tumor shrinkage activity in vivo, an ATC cell line-derived mouse xenograft model was used. Results showed that the combination therapy of HNHA and sorafenib with radiation promoted tumor suppression via caspase cleavage and cell cycle arrest in patient-derived ATC. In addition, the combination therapy of HNHA and sorafenib with radiation was more effective against ATC than therapy with HNHA or sorafenib with radiation. Thus, the combination of HNHA and sorafenib with radiation may be used as a novel curative approach for the treatment of ATC.

scholarly journals Resveratrol and its Nanoparticle suppress Doxorubicin/Docetaxel-resistant anaplastic Thyroid Cancer Cells in vitro and in vivo

2021 ◽  
Vol 5 (2) ◽  
pp. 143-154
Author(s):  
Le Xiong ◽  
Xiao-Min Lin ◽  
Jun-Hua Nie ◽  
Hai-Shan Ye ◽  
Jia Liu
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Cancer Cells

scholarly journals Dehydroxymethylepoxyquinomicin, a Novel Nuclear Factor-κB Inhibitor, Enhances Antitumor Activity of Taxanes in Anaplastic Thyroid Cancer Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5357-5365 ◽  
Author(s):  
Zhaowei Meng ◽  
Norisato Mitsutake ◽  
Masahiro Nakashima ◽  
Dmytro Starenki ◽  
Michiko Matsuse ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Nuclear Translocation ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Anaplastic Thyroid Cancer ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Antitumor Activities

Nuclear factor κB (NF-κB), as an antiapoptotic factor, crucially affects the outcomes of cancer treatments, being one of the major culprits of resistance to chemotherapy. In this study, we investigated whether dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-κB inhibitor, can enhance antitumor activities of taxanes in anaplastic thyroid cancer (ATC) cells. Taxanes induced NF-κB activation in ATC cells, which could compromise the therapeutic effect of the drugs. However, DHMEQ, by inhibiting the nuclear translocation of NF-κB, completely suppressed the DNA binding capacities of NF-κB and lowered the levels of nuclear NF-κB protein. Compared with single treatment (either taxane or DHMEQ), the combined treatment strongly potentiated apoptosis, confirmed by cell survival assay; Western blotting for poly (ADP-ribose) polymerase, caspase 3, X-linked inhibitor of apoptosis, and survivin; and flow cytometry for annexin V. Furthermore, we also demonstrate for the first time that the combined treatment showed significantly greater inhibitory effect on tumor growth in a nude mice xenograft model. These findings suggest that taxanes are able to induce NF-κB activation in ATC cells, which could attenuate antitumor activities of the drugs, but inhibition of NF-κB by DHMEQ creates a chemosensitive environment and greatly enhances apoptosis in taxanes-treated ATC cells in vitro and in vivo. Thus, DHMEQ may emerge as an attractive therapeutic strategy to enhance the response to taxanes in ATCs.

Dsg2-mediated c-Met activation in anaplastic thyroid cancer motility and invasion

2020 ◽  
Vol 27 (11) ◽  
pp. 601-614
Author(s):  
Kyungmin Lee ◽  
Sang-Hyun Lee ◽  
Wooil Kim ◽  
Jangwook Lee ◽  
Jong-Gil Park ◽  
...  
Keyword(s):  
Cell Migration ◽  
Thyroid Cancer ◽  
Distant Metastasis ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Migration And Invasion ◽  
Expression Levels

Anaplastic thyroid cancer (ATC) is a rapidly growing, highly metastatic cancer with limited therapeutic alternatives, thus targeted therapies need to be developed. This study aimed to examine desmoglein 2 (Dsg2) expression in ATC and its biological role and potential as a therapeutic target in ATC. Consequently, Dsg2 was downregulated or aberrantly expressed in ATC tissues. ATC patients with low Dsg2 expression levels also presented with distant metastasis. Dsg2 depletion significantly increased cell migration and invasion, with a relatively limited effect on ATC cell proliferation in vitro and increased distant metastasis in vivo. Dsg2 knockdown induced cell motility through the hepatocyte growth factor receptor (HGFR, c-Met)/Src/Rac1 signaling axis, with no alterations in the expression of EMT-related molecules. Further, specific targeting of c-Met significantly inhibited the motility of shDsg2-depleted ATC cells. Decreased membrane Dsg2 expression increased the metastatic potential of ATC cells. These results indicate that Dsg2 plays an important role in ATC cell migration and invasiveness. Therapies targeting c-Met might be effective among ATC patients with low membrane Dsg2 expression levels, indicating that the analysis of Dsg2 expression potentially provides novel insights into treatment strategies for ATC.

Dual effects for lovastatin in anaplastic thyroid cancer: the pivotal effect of transketolase (TKT) on lovastatin and tumor proliferation

2018 ◽  
Vol 66 (5) ◽  
pp. 1.4-9 ◽  
Author(s):  
Chih-Yuan Wang ◽  
Hao-Ai Shui ◽  
Tien-Chun Chang
Keyword(s):  
Thyroid Cancer ◽  
Cell Growth ◽  
Protein Expression ◽  
Tumor Growth ◽  
Anaplastic Thyroid Cancer ◽  
Control Group ◽  
Cancer Cell Growth ◽  
Protein Levels

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. TKT protein expression in the ARO tumors was assessed using immunohistochemistry analysis. Proteomic analysis revealed that 25 µM lovastatin upregulated TKT expression. Co-treatment of ARO cells with 1 µM lovastatin + 1 µM oxythiamine increased TKT protein expression compared with control levels; however, no differences were observed with 10 µM lovastatin + 1 µM oxythiamine. Furthermore, treatment with either oxythiamine or lovastatin alone reduced ARO tumor expression of TKT, as well as decreased ARO cell proliferation in vitro and tumor growth in vivo. However, mice treated with both lovastatin and oxythiamine at the same time had tumor volumes similar to that of the untreated control group. We conclude that either lovastatin or oxythiamine reduced ARO cell growth; however, the combination of these drugs resulted in antagonism of ARO tumor growth.

scholarly journals Lenvatinib exhibits antineoplastic activity in anaplastic thyroid cancer in vitro and in vivo

2018 ◽  
Author(s):  
Silvia Ferrari ◽  
Guido Bocci ◽  
Teresa Di Desidero ◽  
Giusy Elia ◽  
Ilaria Ruffilli ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Antineoplastic Activity

scholarly journals Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1094
Author(s):  
Caitlin O. Caperton ◽  
Lee Ann Jolly ◽  
Nicole Massoll ◽  
Andrew J. Bauer ◽  
Aime T. Franco
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
In Vitro Models ◽  
Follicular Thyroid Cancer ◽  
Poorly Differentiated

Recent developments in thyroid cancer research have been hindered by a lack of validated in vitro models, allowing for preclinical experimentation and the screening of prospective therapeutics. The goal of this work is to develop and characterize three novel follicular thyroid cancer (FTC) cell lines developed from relevant animal models. These cell lines recapitulate the genetics and histopathological features of FTC, as well as progression to a poorly differentiated state. We demonstrate that these cell lines can be used for a variety of in vitro applications and maintain the potential for in vivo transplantation into immunocompetent hosts. Further, cell lines exhibit differing degrees of dysregulated growth and invasive behavior that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We believe these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and lead to the development of more personalized diagnostic and treatment strategies.

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