RESUMO
BACKGROUND: Survival after resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) still remains poor. Apatinib, a vascular endothelial cell growth factor receptor 2 inhibitor, has been shown to be safe and effective in patients with advanced HCC, so in the present study its efficacy and safety in the adjuvant setting was explored. METHODS: In this single-center, open-label phase II trial, the patients received apatinib (500 mg/day) until they experienced disease recurrence or intolerable toxicity. The primary endpoint was recurrence-free survival (RFS); the secondary endpoints included overall survival (OS) and safety. RESULTS: From a total of 49 patients who were screened between August 2017 and December 2018, 30 study participants received apatinib. According to the Liver Cancer Study Group of Japan classification of PVTT, there were 7, 11, and 12 participants with Vp1, Vp2, and Vp3, respectively. The median duration of treatment was 4.8 months [interquartile range (IQR): 2.0-8.8], and the median dose of apatinib was 339.7 mg/day (IQR: 267.7-500 mg/day). The median follow-up was 14.3 months (IQR: 12.3-19.3). The median RFS was 7.6 months [95% confidence interval (CI): 5.7-9.5 months]. The 1-year RFS rate and the 1-year OS rate were 36.1% and 93.3%, respectively. A total of 29 (96.7%) patients experienced adverse events, and 14 (46.7%) had grade 3 or 4 adverse events. No treatment-related deaths occurred. CONCLUSIONS: Apatinib was well tolerated in patients after resection of HCC with PVTT. The median RFS in this group was improved compared with that previously reported. TRIAL REGISTRATION: No.: NCT03261791 (ClinicalTrials.gov).
RESUMO
BACKGROUND: Triggering receptors expressed on myeloid cells 1 (TREM-1) is a novel molecule that modulates inflammatory responses. Hepatocellular carcinoma (HCC) is a well-known type of inflammation-related cancer. However, TREM-1 expression and its direct effects on HCC cells have not been previously determined. METHODS: Western blotting, quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescence were used to detect TREM-1 expression. TREM-1 upregulation by pcDNA (mammalian expression vector with the CMV promoter) and its downregulation by shRNA (short hairpin RNA) were used to determine the function of this molecule. Transwell, CCK-8, cell cycle, and apoptosis assays were used to detect the effects of TREM-1 on HCC cells. Immunohistochemical staining of samples from a cohort of 322 HCC patients was used to determine the prognostic value of TREM-1. RESULTS: TREM-1 investigation through Western blot, qRT-PCR, and immunofluorescence analyses revealed that TREM-1 was expressed in HCC cells and tumor tissues. Functional experiments suggested that TREM-1 significantly promoted proliferation, invasion, and inhibited apoptosis of HCC cells. Inflammatory cytokine profiles under TREM-1 up- or downregulation indicated the majority of proinflammation cytokines significantly and positively correlated with TREM-1 expression, including IL-1ß, TNF-α, and MCP-1. Western blot analyses revealed that p65, STAT3, ERK, and AKT might be the downstream effectors of TREM-1 signal transduction. High TREM-1 expression correlated significantly with increased recurrence and poorer survival in HCC patients, and it was an independent prognostic factor for recurrence (P = 0.009). CONCLUSIONS: TREM-1 was found to be expressed in HCC cells and to be a prognostic factor for the clinical outcome of HCC.