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The function and mechanism of SYTL5 in papillary thyroid carcinoma (PTC) are still unclear. In this research, we found that SYTL5 was significantly overexpressed in PTC tissues compared with normal thyroid tissues. SYTL5 downregulation significantly weakened the proliferative, migratory, and invasive abilities of PTC cells. In addition, upregulated SYTL5 could promote cancer progression by activating the NF-κB signaling pathway. RAC1b expression is positively associated with SYTL5, and overexpressed RAC1b abrogated the antitumor effect after SYTL5 inhibition. In conclusion, our findings identify the oncogenic role of SYTL5 in PTC by activation of the NF-κB signaling pathway, thus facilitating PTC development and progression.

To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-ai injection (KAI, 康艾注射液) in gastric cancer cells. Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot. KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P

Background The objective of the current study was to investigate the clinical significance of the suprasternal space lymph node (SSLN) in pathological node-positive (pN+) papillary thyroid carcinoma (PTC) patients. Method One hundred and forty patients with pN + PTC who underwent neck dissection were enrolled into this study. SSLN was resected and used as a specimen to investigate the relationship of SSLN with several clinicopathological parameters. Results The metastasis rate of SSLN was 20.7%. On univariate analysis, we found that SSLN metastasis was significantly associated with primary cancer site (inferior portion), strap muscle invasion, level III metastasis, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles. On multivariate analysis, primary cancer site (inferior portion), strap muscle invasion, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles were independent risk factors for SSLN metastasis of PTC. Conclusion For pN + PTC patients, special attention should be paid to the issue of SSLN metastasis.

Shi-Tong Yu,1,* Jun-Na Ge,1,* Jing-Yi Luo,2,* Zhi-Gang Wei,1 Bai-Hui Sun,1 Shang-Tong Lei1 1Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; 2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China *These authors contributed equally to this work Background: Tyrosine kinase inhibitors (TKIs) have been administered to advanced or radioiodine refractory differentiated thyroid carcinoma (RR-DTC) patients for years. We performed a pooled analysis to explore the frequency of severe adverse effects in advanced or RR-DTC patients treated with sorafenib and lenvatinib. Methods: We performed a comprehensive search of computerized databases, including PubMed, Web of Science, Ovid, EMASE, and the Cochrane Library, from the drugs’ inception to July 2018 to identify clinical trials. All grade and severe adverse events (AEs; grade ≥3) were analyzed. This meta-analysis was conducted in accordance with PRISMA guidelines. Results: In total, seve studies published from 2012–2018 with 657 patients were eligible for this study. We included two studies (238 patients) that received 200 mg sorafenib twice and five studies (419 patients) that received 24 mg lenvatinib daily. The frequency of AEs was different among the two drugs. Patients in the sorafenib group had a significantly higher frequency of all grade hand-foot syndrome, hypocalcemia, rash, elevated alanine aminotransferase (ALT), and elevated aspartate aminotransferase (AST). Conversely, the lenvatinib group experienced more frequent all grade voice change, hypertension, nausea, and vomiting compared with those with sorafenib. For grade ≥3 adverse effects, hand-foot syndrome, hypocalcemia, and elevated ALT were more frequent in sorafenib-treated patients. Moreover, lenvatinib-treated patients had a significantly higher incidence of severe weight loss, hypertension, and nausea. Conclusion: Significant differences in common adverse effects, such as all-grade and severe AEs, were detected between sorafenib and lenvatinib in the current study. Early intervention and management of treatment-related AEs (TRAEs) can minimize the impact on patients’ quality-of-life, and avoid unnecessary dose reductions and treatment-related discontinuations. Keywords: sorafenib, lenvatinib, radioiodine-refractory differentiated thyroid carcinoma, RR-DTC, tyrosine kinase inhibitors, TKIs, adverse effects

Background Specific diagnosis and treatment of gastric cancer (GC) require accurate preoperative predictions of lymph node metastasis (LNM) at individual stations, such as estimating the extent of lymph node dissection. This study aimed to develop a radiomics signature based on preoperative computed tomography (CT) images, for predicting the LNM status at each individual station. Methods We enrolled 1506 GC patients retrospectively from two centers as training (531) and external (975) validation cohorts, and recruited 112 patients prospectively from a single center as prospective validation cohort. Radiomics features were extracted from preoperative CT images and integrated with clinical characteristics to construct nomograms for LNM prediction at individual lymph node stations. Performance of the nomograms was assessed through calibration, discrimination and clinical usefulness. Results In training, external and prospective validation cohorts, radiomics signature was significantly associated with LNM status. Moreover, radiomics signature was an independent predictor of LNM status in the multivariable logistic regression analysis. The radiomics nomograms revealed good prediction performances, with AUCs of 0.716-0.871 in the training cohort, 0.678-0.768 in the external validation cohort and 0.700-0.841 in the prospective validation cohort for 12 nodal stations. The nomograms demonstrated a significant agreement between the actual probability and predictive probability in calibration curves. Decision curve analysis showed that nomograms had better net benefit than clinicopathologic characteristics. Conclusion Radiomics nomograms for individual lymph node stations presented good prediction accuracy, which could provide important information for individual diagnosis and treatment of gastric cancer.

In our previous study, we have shown that CRLF1 can promote proliferation and metastasis of papillary thyroid carcinoma (PTC); however, the mechanism is unclear. Herein, we investigated whether the interaction of CRLF1 and MYH9 regulates proliferation and metastasis of PTC cells via the ERK/ETV4 axis. Immunohistochemistry (IHC), qPCR, and Western blotting assays were performed on PTC cells and normal thyroid cells to profile specific target genes. In vitro assays and in vivo assays were also conducted to examine the molecular mechanism. Results showed that CRLF1 directly bound MYH9 to enhance the stability of CRLF1 protein. Inhibition of MYH9 in PTC cells overexpressing CRLF1 significantly reversed malignant phenotypes, and CRLF1 overexpression activated ERK pathway, in vitro, and in vivo. RNA-sequencing revealed that ETV4 is a downstream target gene of CRLF1, which was up-regulated following ERK activation. Moreover, it was revealed that ETV4 is highly expressed in PTC tissues and is associated with poor prognosis. Finally, the ChIP assays showed that ETV4 induces the expression of matrix metalloproteinase 1 (MMP1) by binding to its promoter on PTC cells. Altogether, our study demonstrates that CRLF1 interacts with MYH9, promoting cell proliferation and metastasis via the ERK/ETV4 axis in PTC.

Primary squamous cell carcinoma (PSCC) is a rare neoplasm of the thyroid with a very poor prognosis. We report a case of a 42-year-old woman with occasionally found mass in the right anterior area of the neck. After a total thyroidectomy, histopathology and immunohistochemistry tests confirmed primary squamous cell carcinoma of the thyroid with the exclusion of all other possible primary tumor locations. 5 months later, PET scan discovered abnormality in right cervical lymph nodes with a fine needle aspiration confirming to be tumor recurrence. After a modified radical neck dissection was performed with pathological results of the neoplasms being PSCC of the thyroid origin, a full course consecutive radiotherapy was then followed. Due to a prompt diagnosis and the complete dissection of primary tumor and metastatic lymph nodes, no recurrence was observed at the follow-up visits. Comparing to the published cases of PSCC of the thyroid, our paper stated a whole process of diagnosis and standardized treatment, together with classical matched figures of pre-op examinations and dissected specimen. Furthermore, a review of the present literatures summarized the diagnosis, treatment and prognosis of thyroid PSCC. The management of PSCC requires a multi-disciplinary approach.

Background The recent discovery of cancer/tissue specificity of miRNA has indicated its great potential as a therapeutic target. In Epstein–Barr virus-associated gastric cancer (EBVaGC), host genes are affected by extensive DNA methylation, including miRNAs. However, the role of methylated miRNA in the development of EBVaGC and immune cell infiltration has largely remained elusive. Results After crossmatching the DNA methylation and expression profile of miRNA and mRNA in the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas Research Network (TCGA), we discovered that miR-129-2-3p was significantly suppressed due to hypermethylation on its enhancer in EBVaGC. The differentially expressed genes (DEGs) added up to 30, among which AKAP12 and LARP6 were predicted to be the target genes of miR-129-2-3p and negatively correlated with patients’ survival. Accordingly, miR-129-2-3p was significantly down-regulated in tumor samples in 26 (65%) out of 40 cases in our cohort (P + T cell, macrophage and dendritic cell infiltrates were significantly enriched for the prognostic-indicated hub genes. Conclusion This study has provided a comprehensive analysis of differentially expressed miRNAs and mRNAs associated with genome-wide DNA methylation by integrating multi-source data including transcriptome, methylome and clinical data from GEO and TCGA, QPCR of tumor samples and cell function assays. It also gives a hint on the relationships between methylated miRNA, DEGs and the immune infiltration. Further experimental and clinical investigations are warranted to explore the underlying mechanism and validate our findings.

To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells.Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot.KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P0.01).KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G

Background: Epstein-Barr virus (EBV) is associated with many epithelial malignancies. A few reports on the association between EBV and thyroid tumorigenesis have been investigated. However, the conclusion is highly contradictory. We aimed to explore the role of EBV in thyroid nodule development and its clinical significance in a cohort from southern China. Method: We conducted a retrospective data abstraction study of patients who underwent thyroidectomy between December 2017 and June 2018. We retrospectively analyzed the clinicopathological parameters and EBV infection status (serological antibodies and in situ hybridization). Result: The cohort comprised 384 patients with newly diagnosed thyroid diseases, including 261 papillary thyroid carcinomas, 87 nodular goiters, 21 follicular adenomas, 12 follicular thyroid carcinomas, and 3 medullary thyroid carcinomas. Forty-two (10.9%) patients were identified as being serological antibody positive. However, there was no association between the clinicopathological parameters and serological antibody positivity. Additionally, none of the patients showed EBER expression in thyroid normal/cancer cell nuclei in in situ hybridization. Conclusion: In this study, no correlation between EBV and thyroid diseases was found in a cohort from southern China.

Background: The aim of this study is to evaluate whether radiomic feature-based computed tomography (CT) imaging signatures could predict peritoneal metastasis (PM) in gastric cancer (GC) and to develop a preoperative nomogram for predicting PM status. Methods: We retrospectively analyzed radiomics features of CT images in 955 consecutive patients in pathological T4 gastric cancer from two cancer centers. The prediction model which was built from 292 quantitative image features was developed in the training cohort and validated in internal and external validation cohorts. Lasso regression model was used for feature selection and radiomics signature building. Predicting model was developed by multivariable logistic regression analysis. Radiomics signature, clinical T and N stage were incorporated and presented with a radiomics nomogram. We use calibration, discrimination, and clinical usefulness to assess the performance of the nomogram. Results: The radiomics signature was significantly associated with PM status in training and validation cohorts. Multivariable logistic analysis found the radiomics signature was an independent predictor for peritoneal metastasis. The discrimination accuracies of radiomic signature for predicting PM were 0.751(95%CI, 0.703-0.799), 0.802(95%CI, 0.691-0.912), and 0.745(95%CI, 0.683-0.806) for training cohort, internal and external validation cohort, respectively. Further, the discrimination accuracies of radiomic nomogram for predicting PM were 0.792(95%CI, 0.748-0.836), 0.870(95%CI, 0.795-0.946) and 0.815(95%CI, 0.763-0.867) for training cohort, internal and external validation cohort, respectively. Conclusions: CT-based radiomic signature was a powerful predictor of peritoneal metastasis and the radiomics nomogram could facilitate the preoperative individualized prediction of PM status. Funding Statement: This work was supported by grants from: National Natural Science Foundation of China 81672446, 81600510. The Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (2018J007). Director’s Foundation of Nanfang Hospital, 2016B010. Declaration of Interests: None of the authors had any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations. Ethics Approval Statement: This study was approved by the ethics committee at every participating center, and the informed consent requirement was waived.