Clinical characteristics of thyroid cancer patients with and without type 2 DM.

<p>Tg*: Serum thyroglobulin levels 4 to 6 weeks after thyroidectomy in papillary, follicular, and Hűrthle cell thyroid cancers. Recurrence^#: Percent recurrence1 year after the first thyroid operation.</p

Clinical characteristics of of thyroid cancer patients with type 2 DM who exhibited postoperative progression-free survival or progressive disease.

<p>Tg*: Serum thyroglobulin levels 4 to 6 weeks after thyroidectomy in papillary, follicular and Hűrthle cell thyroid cancers. OHÂ: Treatment with an oral hypoglycemia agent, including 9 cases of combination treatment with insulin.</p

Cancer-specific and postoperative non-progressive survival curves.

<p>Cancer-specific survival curves for patients with type 2 diabetes mellitus (DM), patients without DM (non-DM), and all patients (A). Postoperative non-progressive survival rates for patients with type 2 DM, patients without DM (non-DM), and all patients (B).</p

Multivariate analysis of different parameters related to the mortality of thyroid cancer patients with and without type 2 DM using Cox proportional hazard model.

<p>Tg*: Serum thyroglobulin levels 4 to 6 weeks after thyroidectomy in papillary, follicular and Hűrthle cell thyroid cancer.</p

Age distribution of the subjects.

<p>Age distribution and number of thyroid cancer patients were demonstrated with and without type 2 diabetes mellitus (DM). The percentages of type 2 DM were presented in each age group.</p

Clinical characteristics of survival and mortality groups of thyroid cancer patients with type 2 DM.

<p>Tg*: Serum thyroglobulin levels 4 to 6 weeks after thyroidectomy in papillary, follicular and Hűrthle cell thyroid cancers. OHÂ: Treatment with an oral hypoglycemia agent, including 9 cases of combination treatment with insulin.</p

Dinaciclib decreases the levels of CDK1, cyclin B1 and Aurora A in thyroid cancer cell lines.

(A) The expression of these cell-cycle associated proteins was evaluated by Western blotting in BHP7-13, WRO82-1 and 8505C cells treated with dinaciclib (25 nM) or placebo for the indicated periods. (B) Cells were treated with dinaciclib (25 nM) or placebo for 24 h and stained with fluorescent antibodies against DAPI (blue), cyclin B1 (red) and α-tubulin (green). Cyclin B1 level was significantly reduced after treatment of dinaciclib in prophase cells of BHP7-13, WRO82-1 and 8505C. (C) Cells were treated with dinaciclib (25 nM) or placebo for 24 h and stained with fluorescent antibodies against DAPI (blue), Aurora A (red) and α-tubulin (green). Aurora A level was significantly reduced after treatment of dinaciclib in BHP7-13, WRO82-1 and 8505C cells in prophase. Scale bar, 10 μm.</p

A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer

<div><p>Background</p><p>We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK) inhibitor, in the treatment of thyroid cancer.</p><p>Materials and methods</p><p>Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was assessed using Western blot analysis and immunofluorescence microscopy. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were measured by flow cytometry and fluorometric assay. Mice bearing flank anaplastic thyroid cancer (ATC) were treated with intraperitoneal injections of dinaciclib.</p><p>Results</p><p>Dinaciclib inhibited thyroid cancer cell proliferation in a dose-dependent manner. Dinaciclib had a low median-effect dose (≤ 16.0 nM) to inhibit cell proliferation in seven thyroid cancer cell lines. Dinaciclib decreased CDK1, cyclin B1, and Aurora A expression, induced cell cycle arrest in the G2/M phase, and induced accumulation of prophase mitotic cells. Dinaciclib decreased Mcl-1, Bcl-x_L and survivin expression, activated caspase-3 and induced apoptosis. <i>In vivo</i>, the growth of ATC xenograft tumors was retarded in a dose-dependent fashion with daily dinaciclib treatment. Higher-dose dinaciclib (50 mg/kg) caused slight, but significant weight loss, which was absent with lower-dose dinaciclib (40 mg/kg) treatment.</p><p>Conclusions</p><p>Dinaciclib inhibited thyroid cancer proliferation both <i>in vitro</i> and <i>in vivo</i>. These findings support dinaciclib as a potential drug for further studies in clinical trials for the treatment of patients with refractory thyroid cancer.</p></div

Dinaciclib inhibits subcutaneous xenograft growth of anaplastic thyroid cancer.

<p>(A) The therapeutic effects of dinaciclib were evaluated in mice bearing 8505C flank tumors. Daily intraperitoneal injections of lower-dose (40 mg/kg) and higher-dose (50 mg/kg) dinaciclib significantly repressed 8505C tumor growth after 6 and 4 days when compared with control mice, respectively. (B) Daily treatment of lower-dose dinaciclib did not meaningfully induce weight loss when compared with control mice during the study period. However, higher-dose dinaciclib induced significant weight loss between days 8 and 12. (C) The molecular effects of daily lower-dose dinaciclib (40 mg/kg) treatment were evaluated in 8505C tumors using Western blot analysis. ** <i>P</i> < 0.005 compared with vehicle-treated mice on day 12.</p

Dinaciclib induces cytotoxicity in thyroid cancer cells.

(A) Cytotoxicity was evaluated in cells treated with a series of six 1:1 dilutions of dinaciclib. Dose-response curves were obtained on day 4 using a LDH assay. (B) Median-effect dose (Dm) of dinaciclib on day 4 was calculated for each cell line using CompuSyn software.</p