Search

Hepatocellular carcinoma (HCC) is the most malignant cancer worldwide. Sorafenib (SRF) is a common therapeutic drug used for patients with advanced HCC. Nevertheless, drug resistance frequently occurs in patients treated with sorafenib. Glycyrrhizic acid (GRA) is a natural compound that is identified to exhibit anti-cancer effects. In this work, we aimed to investigate the effects of GRA on SRF-resistant HCC cells and the potential regulatory mechanisms. We established SRF-resistant HCC cell lines and administrated GRA treatment. We performed CCK-8 and colony formation experiments to detect cell proliferation. The accumulation of lipid reactive oxygen species (ROS) and iron levels were measured to evaluate ferroptosis. The protein levels of ferroptosis suppressor glutathione peroxidase 4 (GPX4) and SLC7A11, and the activation of AKT and mTOR were measured with western blotting assay. GRA treatment notably suppressed the viability and proliferation of SRF-resistant HCC cells. SRF-resistant HCC cells exhibited repressed ferroptosis level activated AKT/mTOR cascade, and GRA treatment reversed these effects. Inhibition of ferroptosis and activation of mTOR reversed the anti-proliferation effects of GRA on SRF-resistant HCC cells. Treatment with GRA could effectively reverse the SRF resistance of HCC cells via inducing ferroptosis and inactivating the AKT/mTOR cascade. [ABSTRACT FROM AUTHOR]

Objective: Our aim is to retrospectively compare the disease-free survival (DFS) of adjuvant TACE after surgical resection on patients with tumor less than 5 cm. Methods: A total of 307 patients with HCC underwent hepatic resection between January 2014 to December 2016 were enrolled in this study. Among these, 172 patients underwent surgical treatment only (group A) and 135 patients received surgical resection followed by adjuvant TACE (group B). Propensity score matching (PSM) analysis is used to minimize baseline differences between two groups. DFS was compared between the two groups and Cox proportional hazard model was used to predict the factor for recurrence. Results: Before PSM, the 1, 2, 3 year DFS rate of group A and B were 90.1%, 83.3%, 75.3% versus 85.2%, 73.9%, 68.1%, respectively (p =.286). After PSM, the 1, 2, 3 year DFS rate of group A and group B were 90.3%, 80.8%, 71.9% versus 89.2%, 77.8%, 71.3%, respectively (p =.791). In subgroup analysis where patients presented with microvascular invasion (MiVI), before PSM the 1, 2, 3 year DFS rate were 77.8%, 77.8%, 77.8% and 70%, 70%, 47.3%, for group A and B, respectively (p =.491). After PSM the 1, 2, 3 year DFS rate for group A and B were 71.4%, 71.4%, 71.4% and 100%, 100%, 50%, respectively (p =.440). Cox proportional hazard model identified tumor size ≥3 cm as factor related to recurrence. Conclusions: Adjuvant TACE does not improve the DFS of HCC patients with tumor size less than 5 cm. [ABSTRACT FROM AUTHOR]

Aim: The majority of available data on the clinical efficacy of sunitinib in patients with imatinib-resistant or -intolerant gastrointestinal stromal tumours (GISTs) are from studies of western populations. We investigated the clinical outcomes of imatinib dose escalation versus sunitinib in first-line imatinib-failure Asian GIST patients to further guide clinical treatment. Methods: Patients received imatinib dose escalation and a shift to sunitinib (Group A) or a direct shift to sunitinib (Group B). The objective tumour response was assessed according to Choi's criteria. Progression-free survival (PFS) and overall survival (OS) were calculated. The relationship between genetic mutation and survival was analysed. Results: In total, 40 patients who fulfilled the inclusion criteria were recruited. The differences in survival between Group A and Group B were not significant for PFS (p = .776) or OS (p = .219). For patients with KIT exon 11 mutation, a trend towards a better PFS was found in Group B (p = .122), OS of Group B was better than Group A (p = .013). The median PFS and OS of sunitinib treatment were 8 and 24 months, respectively, and a clinical benefit was observed in 80%. Patients with KIT exon 11 mutations had better PFS compared to those with KIT exon 9 mutations or wild-type GISTs (p = .017, p = .040, respectively). Conclusions: Both imatinib dose escalation and sunitinib were optional in Asian patients after failure of first-line imatinib, and patients with KIT exon 11 mutation benefited more from a direct shift to sunitinib. [ABSTRACT FROM AUTHOR]