Overexpression of interleukin-32α promotes invasion by modulating VEGF in hepatocellular carcinoma.

Interleukin-32α (IL-32α) was reported to exhibit pluripotent pro-inflammatory properties. Recent studies indicate that it promotes the migration and invasion of cancers. We detected the expression of IL-32 in hepatocellular carcinoma (HCC) tissues and investigated its role in tumor angiogenesis and invasion. IL-32α expression in HCC was evaluated by real-time PCR, western blot analysis and immunohistochemical (IHC) staining. Secreted serum IL-32α and VEGF concentrations were detected using a custom-made sandwich ELISA. Furthermore, IL-32α was knocked down in HCC cell lines using siRNA and the cell migration and invasion abilities were assessed. IHC staining showed that IL32α-positive particles were mainly located in the cytoplasm of cancer cells, and it was significantly upregulated in the tumor tissues compared with that in peritumoral tissues. Notably, IL-32α was strongly expressed in perivascular areas. The mean serum concentration of IL-32α in HCC patients was significantly higher than that in the control group (571.45±102.28 vs. 144.60±51.172 pg/ml; P<0.01). Real-time RT-PCR showed that IL-32α mRNA was significantly overexpressed in HCC tumor tissues (IL-32/ß-actin, 15.59±7.8 vs. 3.37±0.47; P<0.01). The in vitro results indicated that IL-32α knockdown inhibited the activation of VEGF-STAT3 signaling in HCC tumor cell lines. IL-32α expression was correlated with clinical relevance in HCC tumor tissues. It is strongly suggested that IL-32α may be a potential predictor of anti-angiogenesis therapy and prognosis of HCC.

Feasibility and safety of sorafenib treatment in hepatocellular carcinoma patients with spontaneous rupture.

AIM: To report the outcome of patients with ruptured hepatocellular carcinoma (HCC) treated at a single center during a 5-year period. METHODS: We retrospectively analyzed 32 patients who presented with ruptured HCC at Shandong Provincial Hospital Affiliated to Shandong University between 2008 and 2013. RESULTS: The mean age of the patients was 53 years (range 39-71 years). Of these patients, 22 received surgical management, 10 underwent transarterial embolization (TAE) or transarterial chemoembolization (TACE), and 12 received sorafenib after surgery, TAE or TACE. Cumulative survival rates at 4, 8 and 12 mo were 72.9%, 50.0% and 33.3%, respectively, in the surgery only group and were 90.0%, 80.6% and 64.1%, respectively, in the surgery plus sorafenib group. Cumulative survival rates at 4, 8 and 12 mo were 68.4%, 43.6% and 19.4%, respectively, in the surgery only or TAE/TACE only groups, and were 91.7%, 75.0% and 60.2%, respectively, in the sorafenib combination groups (P = 0.04). No unexpected side effects due to sorafenib were observed. The most common side effect was hand-foot skin reaction. To date, 5 patients have died. Median follow-up from the start of sorafenib therapy for the remaining 7 patients is 12.7 mo (range 5.8-32.2 mo). CONCLUSION: Sorafenib can be used in patients with ruptured HCC as it has interesting activity and is well tolerated; dose adjustment is generally not required. However, a larger prospective study is necessary to determine the efficacy of sorafenib in this group of patients.

Possible benefit of splenectomy in liver transplantation for autoimmune hepatitis.

Liver transplantation for autoimmune hepatitis (AIH) is usually successful with excellent long-term outcomes, but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy. Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.