FOXM1-CD44 Signaling Is Critical for the Acquisition of Regorafenib Resistance in Human Liver Cancer Cells.

Regorafenib is a multikinase inhibitor that was approved by the US Food and Drug administration in 2017. Cancer stem cells (CSCs) are a small subset of cancer-initiating cells that are thought to contribute to therapeutic resistance. The forkhead box protein M1 (FOXM1) plays an important role in the regulation of the stemness of CSCs and mediates resistance to chemotherapy. However, the relationship between FOXM1 and regorafenib resistance in liver cancer cells remains unknown. We found that regorafenib-resistant HepG2 clones overexpressed FOXM1 and various markers of CSCs. Patients with hepatocellular carcinoma also exhibited an upregulation of FOXM1 and resistance to regorafenib, which were correlated with a poor survival rate. We identified a close relationship between FOXM1 expression and regorafenib resistance, which was correlated with the survival of patients with hepatocellular carcinoma. Thus, a strategy that antagonizes FOXM1-CD44 signaling would enhance the therapeutic efficacy of regorafenib in these patients.

The association between oral health status and the clinical outcome of cirrhotic patients on the waiting list for liver transplantation.

Liver transplantation (LT) candidates often present with poor oral hygiene, which could potentially lead to systemic infections and sepsis owing to their cirrhotic state. In this study, we investigated the oral health status of LT candidates and propose guidance for the detection and treatment of encountered oral lesions among these patients. The decayed, missing, and filled teeth (DMFT) index was determined through oral examination. The presence of dental calculus was detected using panoramic radiography and defined by the radiopaque dental calculus (RDC). From January 2011 to August 2018, 56 LT candidates were enrolled with a median follow-up of 39 months. The overall mean numbers of decayed, missing, and filled teeth among these patients were 2.7 ± 2.8, 10.9 ± 8.3, and 5.4 ± 4.5, respectively. Eighteen patients (32.1%) had RDC. The 5-year survival rates of all 56 patients was 57.7%, while that of those who either received LT (23 patients) or not were 82.1% and 39.8%, respectively. A Cox regression model revealed better overall survival of patients after LT (adjusted hazard ratio [aHR] = 0.067, p = 0.001), worse survival among patients with RDC (aHR = 3.468, p = 0.010), at Child-Pugh stages B and C (aHR for stage B = 11.889, p = 0.028; aHR for stage C = 19.257, p = 0.013) compared to patients at Child-Pugh stage A, and those with a model for end-stage liver disease (MELD) score ≥25 (aHR = 13.721, p = 0.018). This study demonstrates that RDC was associated with worse prognosis in LT candidates. We therefore recommend that interprofessional collaboration should be a routine preoperative procedure for the evaluation of oral hygiene among LT candidates.