A green and simple method for enrichment of major diterpenoids from the buds of Wikstroemia chamaedaphne with macroporous resins and their activation of latent human immunodeficiency virus activity.

In this study, a green and efficient enrichment method for the four majors active diterpenoid components: pimelotide C, pimelotide A, simplexin, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate in the buds of Wikstroemia chamaedaphne was established using macroporous resin chromatography. The adsorption and desorption rates of seven macroporous resins were compared using static tests. The D101 macroporous resin exhibited the best performance. Static and dynamic adsorption tests were performed to determine the enrichment and purification of important bioactive diterpenoids in the buds of W. chamaedaphne. Diterpenoid extracts were obtained by using D101 macroporous resin from the crude extracts of W. chamaedaphne. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated that most of the diterpenoids were enriched in diterpenoid extracts. These results confirmed that diterpenoids in the buds of W. chamaedaphne could be enriched using macroporous resin technology, and the enriched diterpenoid extracts showed more efficient activation of the latent human immunodeficiency virus. This study provides a novel strategy for discovering efficient and low-toxicity latency-reversing agents and a potential basis for the comprehensive development and clinical application of the buds of W. chamaedaphne.

Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne.

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.

Efficacy of therapy for hepatocellular carcinoma with portal vein tumor thrombus: chemoembolization and stent combined with iodine-125 seed.

The purpose of this study is to analyze the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein stent and ¹²5I implantation for the treatment of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma. Fifty-six patients from our department diagnosed with advanced hepatocellular carcinoma with PVTT between January 2008 and December 30, 2010 were divided into two groups. Patients in Group A were treated with TACE and portal vein stent; patients in Group B were treated with TACE, portal vein stent and ¹²5I implantation. The success rate of TACE with portal vein stent and ¹²5I implantation was 100%, with no severe surgery-related complications. After an 8 mo follow-up, the total clinical benefit rates were 56.7 and 88.5% for Groups A and B, respectively (p < 0.05). The median survival times (mOS) for the two groups were 5.7 and 8.9 mo, respectively (p < 0.05). The median time of progression (mTTP) of the two groups were 5.3 and 7.9 mo, respectively (p < 0.05). The 2, 6, 8, 12 and 18 mo patency rates in Group A were 100, 93.3, 83.3, 53.3 and 36.6%. Those in Group B were 100, 100, 92.3, 84.6 and 80.7%. The 2, 6 and 8 mo patency rates showed no statistical differences (p > 0.05), but the 12 and 18 mo rates did (p < 0.05). Our results suggest that TACE combined with portal vein stent and ¹²5I implantation are both safe and effective, and ¹²5I implantation can further postpone the restenosis of the portal vein effectively.

Effects of sorafenib combined with chemoembolization and radiofrequency ablation for large, unresectable hepatocellular carcinomas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation in the treatment of hepatocellular carcinomas larger than 5 cm.</p><p><b>METHODS</b>The treatment of 22 patients with large, unresectable hepatocellular carcinomas (5.0-16.5 cm) treated with sorafenib after transcatheter arterial chemoembolization combined with radiofrequency ablation between 2007 and 2011 was reviewed. The local effects, survival rates, toxicity, and prognostic factors were analyzed.</p><p><b>RESULTS</b>During a follow-up of 9-49 months, 19 patients died and three survived. The median overall survival was 32 months. The overall cumulative 12, 24, and 36-month survival rates were 85.9%, 66.8%, and 23.5% respectively. Technical effectiveness was achieved in 12 out of 28 lesions (42.85%) at the first CT check. The median time to tumor progression was 21 months. The progression-free survival rates at 6, 12, and 24 months were 90.9%, 72.0%, and 38.4%, respectively. Combined therapy was generally well tolerated. There was only one major procedure-related complication, biloma (4.5%). Sorafenib-related adverse events exceeding grade 3 were hand-foot skin reaction (2/22, 9.1%), gastrointestinal hemorrhage (1/22, 4.5%), and diarrhea (2/22, 9.1%). The absence of vascular invasion before treatment was found to be the best prognostic factor in the univariate analysis.</p><p><b>CONCLUSIONS</b>Sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation is a promising approach to the treatment of large, unresectable hepatocellular carcinomas. However, large-scale randomized clinical trials are needed to determine the future role of this treatment.</p>

Transarterial oily chemoembolization combined with interstitial laser thermotherapy for treatment of hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects and adverse effects of transarterial oily chemoembolization combined with interstitial laser thermotherapy (TOCE+ILT) in the treatment of hepatocellular carcinoma.</p><p><b>METHODS</b>Totally 120 patients with hepatocellular carcinoma were randomized into two groups and received interventions with TOCE+ILT or TOCE combined with percutaneous ethanol injection (TOCE+PEI). The treatment was repeated when necessary until the tumor was completely ablated, after which the therapeutic effects were evaluated and the patients were the followed up for observing long-term clinical outcome.</p><p><b>RESULTS</b>Of the 120 patients enrolled in this observation, 105 were followed up for two years (54 in TOCE+ILT group and 51 in TOCE+PEI group). The complete tumor necrosis rate of TOCE+ILT group was significantly higher than that of the TOCE+PEI group (84.8% vs 73.9%,Chi(2)=4.405, P=0.036), and TOCE+ILT was associated with a significantly higher negative conversion rate of AFP positivity (77.8% vs 56.1%, Chi(2)=4.592, P=0.032). The 1-year survival rate were similar between two groups, but the 2-year survival rate was significantly higher in patients with TOCE+ILT (79.6% vs 60.8%, Chi(2)=4.477, P=0.034). The hepatic function was comparable between the two groups before treatment, and 1 week after treatment, the ALT level in patients undergoing TOCE+ILT was significantly lower than that in patients with TOCE+PEI (95.90-/+56.06 U/L vs 116.31-/+45.27 U/L, t=2.04, P=0.043). Post-embolization syndrome was observed in the patients in two groups, but no severe adverse events were found.</p><p><b>CONCLUSION</b>TOCE+ILT has good therapeutic effects and mild side effects in the treatment of hepatocellular carcinoma.</p>

The diagnosis and therapy of intractable upper gastrointestinal hemorrhage caused by hepatic arterioportal vein fistulas in hepatocellular carcinoma / 中华放射学杂志

Objective To investigate the hemodynamics of increasing portal venous pressure(PVP) in hepatocellular carcinoma patients complicated with hepatic arterioportal vein fistulas (HAPVF)and the diagnosis and therapy of intractable upper gastrointestinal hemorrhage caused by HAPVF.Methods One hundred and fifteen cases of hepatocellular carcinoma with upper gastrointestinal hemorrhage were checked by hepatic arteriography and were treated through orifices embolization in cases with severe HAPCF by coils and/or ethanol. Results Twenty-six out of 31 patients suffering intractable upper gastrointestinal hemorrhage have severe HAPVF(the main stem of portal veins are visible).However,there are only 15 patients with light HAPVF among the 84 patients who have mild upper gastrointestinal hemorrhage (the main stem of portal veins are invisible).After the embolization,all of the 26 patients who have severe HAPVF stopped bleeding.Among them,the main stem of hepatic arteries are occluded in 2 patients. Conclusion The existence of severe HAPVF should be taken into consideration when intractable upper gastrointestinal hemorrhage occurs in hepatocellular carcinoma patients,and it can be diagnosed through hepatic artery DSA.Orifice embolization is the most effective method for such kind of hemorrhage.