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10. Sodium-iodide symporter and its related solute carriers in thyroid cancer.

Author

Zhongqin Gong, Minghui Wei, Vlantis, Alexander C., Chan, Jason Y. K., Van Hasselt, C. Andrew, Dongcai Li, Xianhai Zeng, Lingbin Xue, Tong, Michael C. F., and Chen, George G.

Subjects
THYROID cancer, MEMBRANE transport proteins, CELLULAR evolution, CARCINOGENESIS
Abstract

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Autophagy regulates anti-angiogenic property of lenvatinib in thyroid cancer

Author

Xue, Lingbin, Gong, Zhongqin, Vlantis, Alexander C, Chan, Jason YK, Meehan, Katie, van Hasselt, Charles Andrew, Li, Dongcai, Zeng, Xianhai, Wei, Minghui, Tong, Michael CF, and Chen, George G

Subjects
Original Article
Abstract

We aimed to explore the role of lenvatinib-mediated autophagy in papillary thyroid cancer (PTC). K1 and BCPAP, were tested for cell viability, proliferation, and apoptosis after treatment with lenvatinib or chloroquine (CQ) or both. The levels of angiogenesis vascular endothelial growth factor A (VEGFA) were measured by ELISA. Transwell and wound-healing assays were performed using endothelial HUVECs cells. The dynamics of microvessels were detected by tubular formation assay. Western blotting was used to determine the expression of LC3-I/II and Atg-7 and alterations in the PI3K/Akt/mTOR and MEK/ERK pathways. In vivo tumor growth assay and immunohistochemical staining (IHC) was also performed. The results showed that lenvatinib inhibited the viability of K1 and BCPAP cells and caused apoptosis. We further showed that lenvatinib also upregulated autophagy levels in thyroid cancer cells in a dose-dependent manner through the PI3K/Akt/mTOR and MEK/ERK pathways. Co-administration of lenvatinib with CQ resulted in a greater decrease of VEGFA in the tumor supernatant than with either lenvatinib or CQ alone. Autophagy inhibition enhanced the cytotoxicity and anti-angiogenic ability of lenvatinib, which was supported by the HUVECs migration, wound healing, and tube formation assays. Inhibiting autophagy chemically or genetically enhanced lenvatinib’s cytotoxic effects and anti-angiogenic efficacy in thyroid cancer cells in vitro and in vivo. In conclusion, lenvatinib inhibited cell viability and induced apoptosis and autophagy in human PTC cells. Significantly, the combination of lenvatinib and autophagy inhibition may represent a novel and effective treatment option for PTC, which may be able to overcome drug resistance.

Published
2023

37. The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer

Author

Gong, Zhongqin, primary, Yang, Shucai, additional, Wei, Minghui, additional, Vlantis, Alexander C., additional, Chan, Jason Y. K., additional, van Hasselt, C. Andrew, additional, Li, Dongcai, additional, Zeng, Xianhai, additional, Xue, Lingbin, additional, Tong, Michael C. F., additional, and Chen, George G., additional

Published
2022
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47. A scoring model combining serum alpha-fetoprotein and tumor size and number predicts prognosis in hepatitis B virus-related hepatocellular carcinoma patients after curative hepatectomy

Author

Wei, Bai, Chen, Jing-San, Yang, Sheng-Li, Chen, George G., and He, Hao

Subjects
Cancer Research, Oncology, AFP score model, Original Article, Radiology, Nuclear Medicine and imaging, prognosis, Hepatocellular carcinoma (HCC), neoplasms, digestive system diseases
Abstract

Background More in-depth models, such as biomarker and anatomical information, are needed to predict individualized prognoses of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative liver resection. alpha-fetoprotein (AFP) has conflicting value in predicting prognosis. We aimed to investigate the significance of an AFP score model as a potential predictor of prognosis after radical resection in patients with HBV-related HCC. Methods This study retrospectively analyzed 397 patients with HBV-related HCC who underwent hepatic resection between 2001 and 2013. Serum AFP level, tumor size, and tumor number were calculated by adding individual points for the AFP score model. Patient and tumor characteristics were tested for prognostic significance using ANOVA and chi-squared test, respectively. The receiver operating characteristic (ROC) curve was used to identify the AFP score model with or without other risk factors to discriminate patients. Kaplan-Meier and Cox’s analyses were performed to pinpoint risk factors for overall survival (OS) and disease-free survival (DFS) in the patients. Results The cutoff value for the AFP score model was set at 2 using the ROC curve, with good specificity and sensitivity for OS and DFS. According to the AFP score model, 185 patients were in the AFP score >2 group, and 212 were in the AFP score ≤2 group. The median OS in the AFP score ≤2 and AFP score >2 groups were 173.4±1.00 vs. 50.30±8.67 m, respectively (P=0.000). The median DFS in the AFP score ≤2 and AFP score >2 groups were 17.20±3.66 vs. 73.7±10.39 m (P=0.000), respectively. Analyses from Cox’s multivariate proportional hazard model indicated that AFP score (HR =0.563, 95% CI: 0.398–0.798, P=0.001), MVI (HR =0.653, 95% CI: 0.441–0.967, P=0.033), and cirrhosis (HR =0.358, 95% CI: 0.185–0.696, P=0.002) were risk factors for OS. The multivariate Cox model identified MVI (HR =1.589, 95% CI: 1.496–2.854, P=0.003) and AFP score (HR =0.876, 95% CI: 0.404–0.925, P=0.040) as risk factors of DFS. According to the stratification by the AFP score with MVI, the mean OS in the AFP score >2 group combined with the MVI group was significantly shorter, compared with that in the AFP score >2 group without the MVI group (65.58±9.18 vs. 94.21±8.25 m, P=0.024). The mean OS in the AFP score >2 group combined with the cirrhosis group is significantly shorter than that in the AFP score ≤2 group without the cirrhosis group (64.08±7.38 vs. 145.31±8.38 m, P=0.000). Conclusions The AFP score model categorizes HCC patients with relatively good liver function after radical resection with low- and high-risk prognosis.

Published
2019
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