Ibuprofen inhibits anaplastic thyroid cells in vivo and in vitro by triggering NLRP3-ASC-GSDMD-dependent pyroptosis.

Pyroptosis is a novel type of proinflammatory programmed cell death that is associated with inflammation, immunity, and cancer. Anaplastic thyroid carcinoma (ATC) has a high fatality rate, and there is no effective or standard treatment. The disease progresses rapidly and these tumors can invade the trachea and esophagus, leading to breathing and swallowing difficulties. Hence, new treatment methods are greatly needed. Ibuprofen is a common drug that can exert antitumor effects in some cancers. In this study, we demonstrated in vitro and in vivo that ibuprofen can induce ATC pyroptosis. Hence, we treated C643 and OCUT-2C ATC cells with ibuprofen and found that several dying cells presented the characteristic morphological features of pyroptosis, such as bubble-like swelling and membrane rupture, accompanied by activation of ASC and NLRP3 and cleavage of GSDMD. Along with the increased release of LDH, ibuprofen treatment promoted apoptosis and inhibited viability, invasion, and migration. However, overexpression of GSDMD significantly inhibited ibuprofen-induced pyroptosis. In vivo, research has demonstrated that thyroid tumor growth in nude mice can be suppressed by ibuprofen-induced pyroptosis in a dose-dependent manner. In this research, we explored a new mechanism by which ibuprofen inhibits ATC growth and progression and highlighted its promise as a therapeutic agent for ATC.

A novel pharmacological mechanism of anti-cancer drugs that induce pyroptosis.

Pyroptosis is an inflammasome-induced lytic form of programmed cell death, and its main effect involves the release of inflammatory mediators when a cell dies, resulting in an inflammatory response in the body. The key to pyroptosis is the cleavage of GSDMD or other gasdermin families. Some drugs can cause cleavage GSDMD or other gasdermin members cause pyroptosis and suppress cancer growth and development. This review explores several drugs that may induce pyroptosis, thereby contributing to tumor treatment. Pyroptosis-inducing drugs, such as arsenic, platinum, and doxorubicin, were used originally in cancer treatment. Other pyroptosis-inducing drugs, such as metformin, dihydroartemisinin, and famotidine, were used to control blood glucose, treat malaria, and regulate blood lipid levels and are effective tumor treatments. By summarizing drug mechanisms, we provide a valuable basis for treating cancers by inducing pyroptosis. In future, the use of these drugs may contribute to new clinical treatments.

A Clinical Predictive Model of Central Lymph Node Metastases in Papillary Thyroid Carcinoma.

Background: Thyroid carcinoma is one of the most common endocrine tumors, and papillary thyroid carcinoma (PTC) is the most common pathological type. Current studies have reported that PTC has a strong propensity for central lymph node metastases (CLNMs). Whether to prophylactically dissect the central lymph nodes in PTC remains controversial. This study aimed to explore the risk factors and develop a predictive model of CLNM in PTC. Methods: A total of 2,554 patients were enrolled in this study. The basic information, laboratory examination, characteristics of cervical ultrasound, genetic test, and pathological diagnosis were collected. The collected data were analyzed by univariate logistic analysis and multivariate logistic analysis. The risk factors were evaluated, and the predictive model was constructed of CLNM. Results: The multivariate logistic analysis showed that Age (p < 0.001), Gender (p < 0.001), Multifocality (p < 0.001), BRAF (p = 0.027), and Tumor size (p < 0.001) were associated with CLNM. The receiver operating characteristic curve (ROC curve) showed high efficiency with an area under the ROC (AUC) of 0.781 in the training group. The calibration curve and the calibration of the model were evaluated. The decision curve analysis (DCA) for the nomogram showed that the nomogram can provide benefits in this study. Conclusion: The predictive model of CLNM constructed and visualized based on the evaluated risk factors was confirmed to be a practical and convenient tool for clinicians to predict the CLNM in PTC.

Upregulated SLC27A2/FATP2 in differentiated thyroid carcinoma promotes tumor proliferation and migration.

BACKGROUND: Differentiated thyroid carcinoma (DTC) accounts for the vast majority of thyroid cancer (TC) cases. The rapidly increasing incidence of TC requires the urgent identification of new diagnostic and therapeutic targets. Solute carrier family 27 member 2 (SLC27A2/FATP2) plays an essential role in lipid biosynthesis and fatty acid transport. Recent studies have confirmed its involvement in a variety of diseases, including cancer. METHODS: In this study, the expression of SLC27A2 was analyzed in cancer and paracancerous tissue samples from 98 thyroid cancer patients, and we performed ROC analysis to confirm the diagnostic value. CCK8, Transwell, and other methods were used to study its effect on DTC, and the mechanism of SLC27A2 was investigated by RNA sequencing and Western blot. RESULTS: The expression of SLC27A2 was upregulated in both DTC tissues and cell lines and was correlated with clinical progression. In vitro studies further confirmed that SLC27A2 knockdown attenuated the proliferation and invasion of DTC cells. Through RNA sequence analysis and gene set enrichment analysis, we found that the MAPK pathway is the main downstream signaling pathway for the regulation by SLC27A2. SLC27A2 affects cell proliferation and differentiation by inducing changes in the proto-oncogene C-FOS. CONCLUSIONS: Our results show that SLC27A2 plays an important role in tumor proliferation and migration, providing a new putative target for the diagnosis and treatment of TC.

Cep63 knockout inhibits the malignant phenotypes of papillary thyroid cancer cell line TPC­1.

The present study was designed to observe the expression of the centrosomal protein 63 in papillary thyroid cancer (PTC) tissues and cells and to explore the clinical significance of Cep63 expression in PTC. Primary PTC tissues and matched normal thyroid tissues were collected, and the Cep63 expression level was determined by reverse transcription­quantitative PCR and western blotting. A stable Cep63­knockout cell line was constructed to assess the proliferation, invasion, migration and apoptosis abilities in vitro. A subcutaneous tumorigenesis model was established in nude mice to evaluate the effect of Cep63 on tumor growth and proliferation in vivo. Western blotting was used to explore the relevant signaling pathways. The results revealed that the expression level of Cep63 in PTC tissues was significantly increased. The proliferation, invasion and migration abilities of TPC­1 cells were decreased after Cep63 knockout, and silencing of Cep63 resulted in TPC­1 cell cycle arrest in the S phase. Mechanistically, Cep63 knockout inhibited the activation of the Janus kinase/signal transducer and activator of transcription 3 signaling pathway. In conclusion, Cep63 knockout significantly inhibited biological functions of TPC­1 cells in vitro and in vivo, indicating that Cep63 may be an important oncogene of PTC.

Increased Expression of hsa_circ_0002111 and Its Clinical Significance in Papillary Thyroid Cancer.

Circular RNA (circRNA) is a newly discovered non-coding RNA. Recent reports suggest that circRNAs are key regulators of tumorigenesis because of their special structure. In order to investigate the role of hsa_circ_0002111 in papillary thyroid cancer (PTC), we use quantitative real-time polymerase chain reaction (qRT-PCR) to determine the expression pattern of hsa_circ_0002111 in 82 paired PTC and adjacent non-cancerous thyroid tissues. Cell counting kit-8, colony formation, and transwell assays were conducted to assess the effect of hsa_circ_0002111 on PTC cell proliferation, migration, and invasion. We found that the expression of hsa_circ_0002111 was significantly up-regulated in PTC tissues compared with adjacent non-cancerous tissues (P < 0.0001). Expression of hsa_circ_0002111 was also associated with advanced TNM stage and lymph-node metastasis of patients with PTC. The area under the receiver operating characteristic curve was 0.833. Further, cell function assays showed that hsa_circ_0002111 inhibition significantly suppressed the proliferation and invasion abilities of PTC cells in vitro. In conclusions, the study findings show that the over-expression of hsa_circ_0002111 promotes PTC, and thus hsa_circ_0002111 may be a potential diagnostic biomarker and therapeutic target for PTC.

Predictive Values of Inflammation-Related Markers and Thyroid Function in Pediatric Thyroid Cancer Patients.

Few researchers have studied the diagnostic value of inflammation-related hematological indexes of pediatric thyroid carcinoma exclusively. Whether thyroid-stimulating hormone (TSH) is an independent risk factor for pediatric thyroid cancer is still controversial. To assess the correlativity and predictive values of inflammation-related markers and thyroid function in pediatric thyroid cancer patients, we collected a total of 270 children with thyroid nodules for two consecutive years. Clinical data including age, gender, thyroid function, inflammation indexes, and clinical pathologic finding were collected and analyzed. The above-mentioned data were compared between the benign group and the malignant group, followed by the subgroups comparison. Binary logistic regression analysis was used to evaluate the correlation of markers and the pathological features of thyroid nodules. The neutrophil-to-lymphocyte ratio (NLR) showed a significant difference between thyroid cancer and thyroid nodules, while TSH did not. NLR > 1.49529 was the prognostic indicator of pediatric thyroid cancer. The logistic regression model further revealed that NLR > 1.49529 was an independent risk factor for thyroid cancer in pediatric patients. Furthermore, TSH was not correlated with the tumor characteristics in the thyroid cancer group. In conclusion, the findings in this study showed that NLR could be a predictor of thyroid cancer in pediatric patients and refuted the present view that TSH is a risk factor in pediatric thyroid cancer.

The Role of Exosomes in Thyroid Cancer and Their Potential Clinical Application.

The incidence of thyroid cancer (TC) is rapidly increasing worldwide. The diagnostic accuracy and dynamics of TC need to be improved, and traditional treatments are not effective enough for patients with poorly differentiated thyroid cancer. Exosomes are membrane vesicles secreted specifically by various cells and are involved in intercellular communication. Recent studies have shown that exosomes secreted by TC cells contribute to tumor progression, angiogenesis and metastasis. Exosomes in liquid biopsies can reflect the overall molecular information of tumors, and have natural advantages in diagnosing TC. Exosomes also play an important role in tumor therapy due to their special physicochemical properties. TC patients will benefit as more exosome patterns are discovered. In this review, we discuss the role of TC-derived exosomes in tumorigenesis and development, and describe the application of exosomes in the diagnosis and treatment of TC.