Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression.

Daphne genkwa, a Chinese medicinal herb, is used frequently in Southeast Asian countries to treat diseases; the flavonoid hydroxygenkwanin (HGK) is extracted from its flower buds. The bioactivity of HGK, particularly as an anti-liver cancer agent, has not been explored. In this study, human hepatocellular carcinoma (HCC) cell lines and an animal xenograft model were employed to investigate both the activity of HGK against liver cancer and its cellular signaling mechanisms. HCC cells treated with HGK were subjected to cell function assays. Whole transcriptome sequencing was used to identify genes whose expression was influenced by HGK, and the flavonoid's cancer suppression mechanisms were further investigated through gain- and loss-of-function assays. Finally, in vitro findings were tested in a mouse xenograft model. The data showed that HGK induced the expression of the microRNA miR-320a, which in turn inhibited the expression of the transcription factor 'forkhead box protein M1' (FOXM1) and downstream FOXM1-regulated proteins related to epithelial-mesenchymal transition, thereby leading to the suppression of liver cancer cell growth and invasion. Significant inhibition of tumor growth was also observed in HGK-treated mice. Hence, the present study demonstrated the activity of HGK against liver cancer and validated its potential use as a therapeutic agent.

The efficacy and safety of concentrated herbal extract granules, YH1, as an add-on medication in poorly controlled type 2 diabetes: A randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. METHODS: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation. RESULTS: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of ß cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. CONCLUSIONS: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and ß-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

Operative strategy for follicular thyroid cancer in risk groups stratified by pTNM staging.

This study determined cancer survival rates and follow-up status at different pTNM stages to stratify risk groups in follicular thyroid carcinoma. Two hundred and fourteen follicular thyroid cancer patients (167 females, 47 males) who underwent surgery and followed-up treatment at a single medical center were enrolled in this retrospective study. Tumors were staged by UICC-TNM criteria (6th edition). Low risk for follicular thyroid cancer was defined as pT1N0M0. (Moderate-risk group) was defined as all other patients in pTNM stage I, and high risk as patients in stages II-IV. After mean follow-up of 9.6+/-0.3 years, 1.6% (2/120), 21.9% (7/32), 5.6% (1/18) and 52.3% (23/44) of patients in pTNM stages I-IV, respectively, died of thyroid cancer. Of 214 follicular thyroid cancer patients, 35 (16.4%), 85 (39.7%) and 94 (43.9%) were defined as low-, moderate- and high-risk groups at the time of surgery. None of the low-risk patients died, and all achieved disease-free status. In the moderate- and high-risk groups, 2.4% (2/85) and 27.7% (26/94) died of thyroid cancer. The moderate- and high-risk groups underwent near-total thyroidectomy and (131)I therapies, and 15 of 107 (14.9%) died of thyroid cancer while 18 (16.8%) had persistent disease at the end of the study period. Multiple regression analysis demonstrated that tumor size, radioactive iodide therapy and post-operative thyroglobulin level significantly differ between the mortality and survival groups. In conclusion, the low-risk follicular thyroid cancer group as defined by pTNM staging had excellent prognosis. Total thyroidectomy and post-operative radioactive iodide therapy are mandatory in moderate- and high-risk groups. Over one-fourth of the follicular thyroid cancer patients in the high-risk group died of thyroid cancer despite aggressive treatment.

An aberrant autocrine activation of the platelet-derived growth factor alpha-receptor in follicular and papillary thyroid carcinoma cell lines.

Platelet-derived growth factor receptor (PDGFR) can bind to its ligand and consequently possess a kinase activity, and which is associated with the carcinogenesis of different cell types, including astrocytomas, oligodendrogliomas, and glioblastoma. In a cDNA microarray analysis, we observe the over-expressed mRNA of both PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells. And the elevated protein expressions of PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells were also confirmed by a Western blot analysis. The phosphorylation of PDGF-alpha receptor evaluated by an antibody against Tyr 720-phosphate was found in thyroid carcinoma cells. The tyrosine kinase activity of PDGF-alpha receptor was inhibited by tyrphostin AG1295 and showed a dose-dependent inhibition for the proliferation of thyroid carcinoma cells. These findings imply that autocrine activation of PDGF-alpha receptor plays a crucial role in the carcinogenesis of thyroid cells.