Children and adolescents with differentiated thyroid cancer from 1998 to 2018: a retrospective analysis.

OBJECTIVES: This study aims to investigate the clinical features of differentiated thyroid carcinoma (DTC) in children and adolescents under 18 years and assess the impact of surgery combined with thyroid hormone and radioactive iodine (RAI) on their prognosis. METHODS: A retrospective observational study was conducted, involving children/adolescents with DTC who underwent surgery at the Head and Neck Department of Tianjin Medical University Cancer Institute and Hospital from January 1998 to December 2018. RESULTS: Among 198 patients, 130 (65.7 %) were female. According to the American Thyroid Association guidelines, cases were categorized as low (106, 53.5 %), intermediate (54, 27.3 %), and high (38, 19.2 %) risk. The follow-up duration ranged from 3 to 23 years. Local recurrence and distant metastasis were identified in 21 (10.6 %) and 14 (7.1 %) cases, respectively. All patients received levothyroxine, while RAI therapy was administered to intermediate- and high-risk patients. The local recurrence and distant metastasis rates in these two groups were 33.3 and 39.5 %, respectively, with no recurrence or metastasis in the low-risk group. Persistent without structural evidence of disease were 0.9, 3.7, and 26.3 % at end of follow-up for the low-, intermediate-, and high-risk groups, respectively. The overall survival rates for all three groups were 100 %, while disease-free survival rates were 99.1, 63.0, and 34.2 % for the low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: Children/adolescents with low-risk DTC exhibited a favorable prognosis even without RAI. However, intermediate- and high-risk DTC patients, despite RAI and levothyroxine treatment, showed elevated rates of persistent disease, local recurrence, and distant metastasis.

Cinnamomi Ramulus inhibits the growth of colon cancer cells via Akt/ERK signaling pathways.

BACKGROUND: Colon cancer (CC) ranks the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancer has recently attracted increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism against CC needs to be fully evaluated. METHODS: TCMSP and China National Knowledge Infrastructure database were utilized to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. We subsequently evaluated the therapeutic effect of CR by orally administrating it on CC-bearing mice. Next, we further identified the potential CC-related targets by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis results were validated by a series of cellular functional and molecular biological assays. UPLC-MS/MS method and molecular docking analysis were employed to identify the potential key components from CR. RESULTS: In this study, we firstly found that CR has potential therapeutic effect on cancer. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, while inhibiting the viability and motility of CC cells in vitro. We obtained 111 putative core therapeutic targets of CR. Subsequent enrichment analysis on these targets showed that CR could induce apoptosis and cell cycle arrest in CC cells by blocking Akt/ERK signaling pathways, which was further experimentally verified. We identified 5 key components from the crude extract of CR, among which taxifolin was found most likely to be the key active component against CC. CONCLUSIONS: Our results show that CR as well as its active component taxifolin holds great potential in treatment of CC.

Perfluorooctanoic acid induces hepatocellular endoplasmic reticulum stress and mitochondrial-mediated apoptosis in vitro via endoplasmic reticulum-mitochondria communication.

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant that is widely distributed in the natural environment. Cohort study showed that PFOA-producing workers displayed a significant increase for mortality of liver cancer and liver cirrhosis. However, the underlying mechanism of PFOA-induced hepatotoxicity is far from clear. In this research, cell viability, apoptosis rate, reactive oxygen species, mitochondrial membrane potential (ΔΨm), calcium ion levels, and protein expressions of human liver L02 cells in response to PFOA were determined. Results indicated that a 24 h-treatment with 64 and 256 µM PFOA could remarkably induce mitochondrial-mediated apoptosis via initiating the vicious cycle between endoplasmic reticulum stress and oxidative stress, thereby increasing the level of calcium ion and decreasing the level of ΔΨm, simultaneously elevating the protein expressions of Cyclophilin D (CYPD), Bcl-2 homologous antagonist/killer (Bak), Bcl-2-associated X protein (Bax), Bcl-2-like protein 11 (Bim), cytochrome C (Cyt-C), 78 kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and thioredoxin-interacting protein (TXNIP), while inhibiting the protein expression of tumor necrosis factor receptor-associated protein 1 (TRAP1), Lon protease 1 (Lonp1), Pro-caspase-9, B-cell lymphoma-2 (Bcl-2), and Sigma 1-type opioid receptor (Sig-1R) (p < 0.05). To sum up, PFOA-induced hepatocellular endoplasmic reticulum stress and mitochondrial-mediated apoptosis in vitro was regulated by endoplasmic reticulum (ER)-mitochondria communication via mitochondria-associated ER membranes (MAMs).