Podoplanin promotes cancer-associated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer.

BACKGROUND: Podoplanin (PDPN) is a transmembrane glycoprotein that mediates tumor cell-induced platelets aggregation in different cancer types. Emerging data indicate that PDPN is a marker for poor prognosis of human oral squamous cell carcinoma (OSCC). However, the functional impacts of PDPN on cancer formation and disease progression of OSCC remain to be elucidated. METHODS: The sublines of the OECM-1 oral cancer cells with PDPN knockdown or overexpression were established. The cellular characteristics and the ability to induce platelet aggregation of these cells lines were analyzed. An ectopic xenograft animal model by inoculating cancer cells into the anterior neck region of nude mice was established to investigate the functional impact of PDPN on disease progression and cancer-associated thrombosis of OSCC. RESULTS: PDPN promoted OSCC cell migration and invasion, but had no effect on cell proliferation in vitro and tumor growth in vivo. Co-incubation of PDPN-positive (PDPN+) OSCC cells with platelets induced platelet activation and aggregation. The mice bearing PDPN+ tumor had a decrease in overall survival despite that there was no gross appearance of distant metastasis. A speckled immunofluorescence staining pattern of platelet marker mCD41 was defined in the PDPN+ tumor sections and the intensity was greater than in the PDPN-low or negative tumor sections. Co-immunofluorescence staining of the tumor sections with mCD41 and the endothelial cell marker mCD31 further demonstrated that platelet aggregates were located in the lumen of blood vessel and were also distributed intratumorally in the mice bearing PDPN+ tumors. CONCLUSIONS: These data demonstrated that PDPN expression in the cancer cells is associated with high risk of thrombosis, leading to unfavorable overall survival of the mice. This study provides new insights into the functions of PDPN in cancer-associated thrombosis and in the pathophysiology of OSCC.

Short-term prediction of extremely hot days in summer due to climate change and ENSO and related attributable mortality.

Summer days with extremely hot temperatures in Taiwan have been increasing for the past few decades, and this continuing trend is expected to worsen heat-related mortality. To mitigate the corresponding health impacts, in this study, we developed a statistical state-space model to predict the number of extremely hot days in June-September for the next year. Based on historical data from 1951 to 2017, we estimated the climate change trend after adjusting for the nonlinear lagged effect of the Niño 3.4 index. We then developed a predictive state-space model using these two primary factors and adjusting for residual autocorrelations. Validation results comparing the extremely hot days observed over 2015-2017 with predictions showed that 86% of the average prediction errors were within 4 days of the observations. To assess the health impacts, we applied the model to the projection of heat-attributable mortality (AM) in 2018 by adopting a comparative risk assessment (CRA) approach with the reference period of 2001-2010. The results showed that the Taipei metropolitan area in northern Taiwan is the most affected region with AM of 1501 deaths from all-causes, followed by Taichung in central Taiwan with 490 deaths. The prediction model and the CRA projection provide both a tool and guidance for public health administrators to address the imminent threat posed by climate change.

Circulating Epithelial Cell Characterization and Correlation with Remission and Survival in Patients with Thyroid Cancer.

BACKGROUND: Thyroid cancer is the most common endocrine tumor and generally has relatively good clinical outcomes. However, 15-20% of patients ultimately develop recurrence or disease-related death. The appropriate prognostic factors for thyroid cancer are still elusive. This study evaluated whether the number of circulating tumor cells/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin receptor (TSHR) is related to remission and disease-specific mortality (DSM) of patients with thyroid cancer. METHODS: Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched by lysis of red blood cells and depletion of leukocytes. Subtyping and quantification of the enriched cells were performed with immunofluorescence staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether the number of a specific subtype of CECs is related to remission and DSM of patients was determined by univariate and multivariate analyses. RESULTS: The EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts for patients in the non-remission group (n = 43) were significantly higher when compared to the remission group (n = 85; p < 0.001). Receiver operating characteristic analysis showed that the number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was able to distinguish the status of remission from non-remission. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 40, 47, and 14 (cells/mL), with the accuracy of the assay equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM+-CECs (p < 0.001), PDPN+-CECs (p = 0.013), and TSHR+-CECs (p < 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). Receiver operating characteristic analysis showed that EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts were able to distinguish mortality from survival status. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 27, 25, and 9 (cells/mL), with the accuracy of the assay equivalent to 69.5%, 67.2%, and 68.5%, respectively. CONCLUSIONS: CEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.