BACKGROUND:To investigate reasonable treatment modalities and prognostic factors for patients with differentiated thyroid carcinoma (DTC) bone metastases (BM).METHODS:The clinicopathological characteristics and follow-up data for all patients with DTC BM who received treatment in the Third Affiliated Hospital of Kunming Medical University between November 1, 1993 and December 31, 2016 were analyzed retrospectively with respect to mortality and survival rates. Multivariate analysis was performed using the Cox proportional hazard model.RESULTS:The 5- and 10-year overall survival (OS) rates were 51.5% and 17.2%, respectively, for all 60 patients. Univariate analysis showed that patients diagnosed with BM at <45 years of age, with controlled thyroid-stimulating hormone (TSH) levels and those undergoing surgery or 131I therapy had better prognoses. Patients with cervical vertebra metastases, multiple organ metastases other than bone, and those receiving chemotherapy had worse prognoses. Gender, pathological type, number of BM lesions, skeletal-related events (SREs) and whether or not the patient received radiotherapy were not related to prognosis. Cox regression analysis showed that age at diagnosis of BM, undergoing surgery for bone lesions, and not receiving chemotherapy were independent factors of favorable prognosis for patients with DTC BM.CONCLUSIONS:Patients with DTC BM have poor prognoses. Age at diagnosis with BM <45 years old, undergoing surgery for bone lesions, and not receiving chemotherapy were independent factors of favorable prognosis for patients with DTC BM. 131I combined with surgery for bone metastatic lesions may be the best treatment model for most patients with DTC BM disease.

Abstract Background Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. In a preliminary study, we demonstrated that some hematopoietic factors may be involved in the progression of ATC. The adaptor protein LNK, which is a negative regulator of hematopoietic cytokine signalling, has been studied extensively in malignant hematopoietic cells. However, there are few studies on LNK in solid tumours. Methods Real-time PCR, immunohistochemistry (IHC) and western blot analysis of LNK were performed on ATC cells, differentiated thyroid cancer (DTC) cells and normal thyroid cells. In vitro assays (including pull-down, liquid chromatography-mass spectrometry (LC–MS), co-IP, MTT and colony formation) were performed to validate the effect of LNK on ATC progression and elucidate the molecular mechanisms. Results Compared with DTC cells and normal thyroid cells, ATC cells exhibit overexpression of LNK. In addition, LNK overexpression results in increased proliferation of ATC cells. Conversely, LNK knockdown significantly suppresses ATC cell proliferation. LC–MS identified the 14-3-3 ε/γ protein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ε/γ binding. Conclusions The present study elucidated the important role of LNK in the growth of ATC opposite to its behaviour in the hematopoietic system and indicates that LNK is a potential target for the treatment of ATC.

Objective To explore the mechanism of hypoxia inducing interleukine (IL)-11 secretion in anaplastic thyroid carcinoma (ATC) cells and the mechanism of IL-11 promoting epithelial mesenchymal transition of ATC cells.Methods Knockdown of IL-11,hypoxia-inducible factor (HIF)-1α in ATC cells or treatment of ATC cells with Cobalt Chloride,recombinant human interleukin (rhIL)-11,IL-11 antibody,then the effects of these interventions on the invasion and migration ability of ATC cells and its mechanism were detected by enzyme-linked immunosorbent assay (ELISA),Transwell,Real-time polymerase chain reaction (PCR),Western blotting.Results Under treatment with Cobalt Chloride,the protein and mRNA expression of IL-11 increased in ATC cells.The number of invasive cells in the knockdown HIF-1α group (61.7 ±4.9,30.0 ±4.6) was less than that of the control group 261.7 ± 8.7 (P ＜ 0.01),and the number of migrated cells (87.3 ± 4.5,73.8 ± 5.4) was less than the control group 337.3 ± 7.1 (P ＜ 0.01).The expression ofphosphorylated Akt (p-Akt),phosphorylated glycogen synthase kinase 3β (p-GSK3β) and Snail protein was significantly increased after treatment with rhIL-11.The protein expression of p-Akt,p-GSK3β and Snail were significantly decreased after knockdown of IL-11 expression in ATC cells.Conclusion Hypoxia induced epithelial mesenchymal transition of ATC cells is the main mechanism of high invasion and migration of ATC cells.

Platelet counts have been reported to be closely related to distant metastasis of many malignant tumors. Our previous study showed that elevated peripheral blood platelet counts may be an adverse prognostic factor of anaplastic thyroid carcinoma (ATC) patients, indicating that platelets may promote ATC progression. In the present study, we aimed to identify the role of platelets in ATC cell invasion and migration and to explore the underlying mechanisms. We found that platelets can promote the invasive and migratory of ATC cells, which may be related to the interaction between activated platelet-secreted chemokine (C-C motif) ligand 3 (CCL3) and its receptor CCR5. The interaction was shown to induce the upregulation of matrix metalloproteinase (MMP)-1 via NF-κB pathway. These findings could provide a new idea for the research of targeted platelets to inhibit tumor metastasis.

The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1. Furthermore, we found that cisplatin resistance of TSCC cells was related to cisplatin inducing lysosome biogenesis in a TFEB-dependent manner, which was regulated by c-Abl. In summary, this is the first study to show that Bafilomycin A1 increases the sensitivity of TSCC cells to cisplatin by inhibiting lysosomal function but not autophagy. Lysosomes may be a potential target to increase cisplatin cytotoxicity toward TSCC cells.