ObjectiveTo explore the role of β-catenin in the proinvasive consequences of hypoxia in hepatocellular carcinoma (HCC).MethodsWe established in vitro and in vivo hypoxic models using the highly metastatic MHCC97 and the stable red fluorescent protein-expressing MHCC97-R cells.The role of β-catenin in hypoxia-mediated aggressiveness was investigated by β-catenin knockdown.ResultsHypoxia caused a pronounced arrest of proliferation in MHCC97 cells,suppressed tumor growth in MHCC97-R xenografts,but promoted in vitro invasiveness and in vivo metastasis.β-Catenin-silencing by short hairpin significantly inhibited the enhanced invasiveness of MHCC97 cells due to hypoxia,reduced the increase in distant metastasis by hepatic arterial ligation,but failed to further restrain cell proliferation.Conclusionβ-Catenin in HCC cells plays an essential role in the hypoxia-induced metastatic potential.A reduction of βcatenin expression inhibited the proinvasive consequences of hypoxia in HCC.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM. METHODS: A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT. RESULTS: The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%). CONCLUSIONS Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Cisplatin/therapeutic use* ; Humans ; Lung Neoplasms/drug therapy* ; Mesothelioma/drug therapy* ; Mesothelioma, Malignant ; Neutropenia ; Pemetrexed/therapeutic use* ; Platinum/therapeutic use* ; Pleural Neoplasms/drug therapy*