Dataset Information

Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer.

ABSTRACT: Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment reduced cells in the S phase and increased cells in the G2/M phase. Volasertib activated caspase-3 activity and induced apoptosis. Drug combinations of volasertib and sorafenib showed mostly synergism in four well-differentiated thyroid carcinoma cell lines in vitro. Volasertib treatment in vivo retarded the growth of a papillary thyroid tumor model. Furthermore, the combination of volasertib with sorafenib was more effective than a single treatment of either in a follicular thyroid cancer xenograft model. Promising safety profiles appeared in animals treated with either volasertib alone or volasertib and sorafenib combination therapy. These findings support volasertib as a potential drug for the treatment of patients with WDTC.

SUBMITTER: Lin SF

PROVIDER: S-EPMC7475022 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer.

Lin Shu-Fu SF Lin Jen-Der JD Yeh Chun-Nan CN Huang Yu-Tung YT Chou Ting-Chao TC Wong Richard J RJ

Endocrine-related cancer 20190801 8

Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment red ...[more]

PMID: 31189135

Similar Datasets

Project description:BackgroundSurgical extent in the management of well-differentiated thyroid cancer (DTC) remains a recurrent subject of debate. This is especially relevant in low-risk DTC of 1-4 cm, which represent the majority of new thyroid cancer diagnoses. With trends towards treatment de-escalation and recent guidelines from the American Thyroid Association and British Thyroid Association endorsing hemithyroidectomy (HT) alone for low-risk DTC of 1-4 cm, we sought to systematically appraise the literature to examine recurrence rate outcomes after HT in this low-risk group.SummarySearching PubMed, Cochrane Library, and Ovid MEDLINE, we conducted a systematic review to assess the survival and recurrence rate data presented in all published studies that had a cohort of patients treated with HT for the treatment of DTC. Pooled 10-year survival and recurrence rates, odds ratios, and 95% confidence intervals were calculated for meta-analysis. We identified 31 studies (with a total of 228,746 patients (HT: 36,129, total thyroidectomy, TT: 192,617), which had published recurrence and/or survival data for patients having had HT for DTC. We discovered a pooled recurrence rate of 9.0% for HT, which is significantly higher than in previously published reports. Further, this rate is maintained when examining patients within low-risk cohorts established with recognised risk classifications. We also discovered that of those patients who develop recurrent disease, 48% recur outside the central neck.Key messagesOur study provides a comprehensive systematic review of evidence aimed primarily at defining the recurrence rate in DTC after HT, and more specifically within the low-risk subgroup. We describe pooled recurrence and 10-year survival rates from a larger, broader, and more contemporary patient population than has been previously reported. Our findings indicate that there is a small but significantly higher recurrence rate after HT than TT, but the evidence base is heterogenous and subject to confounding factors and would ultimately benefit from prospective randomised trials to overcome these deficiencies.

Project description:BACKGROUND: The preoperative characterization of thyroid nodules is a challenge for the clinicians. Fine-needle aspiration (FNA) is the commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. There is an urgent need to identify biomarkers that could be used with the FNA to distinguish benign thyroid nodules from malignant tumors. The purpose of the study is to examine the level of expression of the helicase-like transcription factor (HLTF) in relation to neoplastic progression of thyroid carcinomas. METHODS: The presence of HLTF was investigated using quantitative and semi-quantitative immunohistochemistry in a series of 149 thyroid lesion specimens. Our first clinical series was composed of 80 patients, including 20 patients presenting thyroid adenoma, 40 patients presenting thyroid papillary carcinoma, 12 patients presenting thyroid follicular carcinoma and 8 patients presenting anaplastic carcinoma. These specimens were assessed quantitatively using computer assisted microscopy. Our initial results were validated on a second clinical series composed of 40 benign thyroid lesions and 29 malignant thyroid lesions using a semi-quantitative approach. Finally, the HLTF protein expression was investigated by Western blotting in four thyroid cancer cell lines. RESULTS: The decrease of HLTF staining was statistically significant during thyroid tumor progression in terms of both the percentage of mean optical density (MOD), which corresponds to the mean staining intensity (Kruskall-Wallis: p < 0.0005), and the labelling index (LI), which corresponds to the percentage of immunopositive cells (Kruskall-Wallis: p < 10-6). Adenomas presented very pronounced nuclear HLTF immunostaining, whereas papillary carcinomas exhibited HLTF only in the cytoplasm. The number of HLTF positive nuclei was clearly higher in the adenomas group (30%) than in the papillary carcinomas group (5%).The 115-kDa full size HLTF protein was immunodetected in four studied thyroid cancer cell lines. Moreover, three truncated HLTF forms (95-kDa, 80-kDa and 70-kDa) were also found in these tumor cells. CONCLUSIONS: This study reveals an association between HLTF expression level and thyroid neoplastic progression. Nuclear HLTF immunostaining could be used with FNA in an attempt to better distinguish benign thyroid nodules from malignant tumors.

Dataset Information

Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer.

Publications

Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets