Unresectable hepatocellular carcinoma: transarterial chemoembolisation plus Huachansu - a single-center randomised controlled trial.

OBJECTIVE: Huachansu, a Chinese medicine derived from the dried skin glands of toad venom, has been used in China since the 1970s to treat liver cancer. Transarterial chemoembolisation (TACE) is the standard of care for patients with unresectable hepatocellular carcinoma (HCC). This study evaluated the efficacy and safety of the combination of TACE and Huachansu in unresectable HCC. METHODS: From September 2012 to September 2016, 120 patients diagnosed with unresectable HCC were prospectively enrolled. Patients were randomised at a 1:1 ratio into the combined treatment group (Huachansu-TACE) and the TACE treatment group. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS) and safety. The exploration outcome serum Na+/K+-ATPase (NKA) α3 at baseline and 3-month follow-ups were compared for a prognostic role. All patients were subjected to 36-month follow-up. RESULTS: A total of 112 patients who completed the study were included in the analysis. PFS and OS were significantly better in the Huachansu-TACE group than in the TACE group (p=0.029 and p=0.025, respectively), with a median PFS of 6.8 and 5.3; and a median OS of 14.8 months and 10.7 months, respectively. Although no prognostic significance was found between the baseline NKA-low and NKA-high groups in the patients' OS (p=0.48), its changes after 3-month follow-up showed significant prognostic values, of which, were 8.5 months and 23.8 months, respectively (p<0.001). Treatment-related adverse events were comparable between groups. CONCLUSIONS: Huachansu-TACE is effective in prolonging the PFS and OS in patients with unresectable HCC. TRIAL REGISTRATION NUMBER: NCT01715532.

Bufalin Inhibits Tumorigenesis and SREBP-1-Mediated Lipogenesis in Hepatocellular Carcinoma via Modulating the ATP1A1/CA2 Axis.

Altered lipid metabolism is a hallmark of hepatocellular carcinoma (HCC), a common malignancy with a dismal prognosis against which there is a lack of effective therapeutic strategies. Bufalin, a classical Na[Formula: see text]-K[Formula: see text]-ATPase (NKA) inhibitor, shows a potent antitumor effect against HCC. However, the role of bufalin in regulating lipid metabolism-related pathways of HCC remains unclear. In this study, we examined the interaction between bufalin and its target molecule, ATP1A1/CA2, in vitro and in vivo and explored the intersected downstream pathways in silico. A multi-omics analysis of transcriptomics and metabolomics was employed to screen for potential action targets. The results were verified and correlated with the downstream lipid de novo synthesis pathway and the bufalin/ATP1A1/CA2 axis. We found that bufalin suppressed the ATP1A1/CA2 ratio in the treated HCC cells and showed a negative correlation with bufalin drug sensitivity. Functionally, ATP1A1 overexpression and CA2 down-regulation inhibited the bufalin-suppressed HCC proliferation and metastasis. Furthermore, down-regulation of CA2 induced epithelial-mesenchymal transition and bufalin resistance in HCC cells by up-regulating ATP1A1. Mechanistically, lipid metabolism-related signaling pathways were enriched in low ATP1A1 and high CA2 expression subgroups in GSEA. The multi-omics analysis also showed that bufalin was closely related to lipid metabolism. We demonstrated that bufalin inhibits lipogenesis and tumorigenesis by down-regulating SREBP-1/FASN/ACLY via modulating the ATP1A1/CA2 axis in HCC.

High-intensity focused ultrasound enhances the effect of bufalin by inducing apoptosis in pancreatic cancer cells.

PURPOSE: High-intensity focused ultrasound (HIFU) has the potential to be an effective therapeutic strategy for pancreatic cancer (PC). However, owing to the high malignancy and poor prognosis of PC, the use of HIFU therapy alone is not sufficient to impair the progression of PC. Bufalin, a compound extracted from traditional medicine, is known to inhibit the growth and progression of PC cells. However, the effect of the combination therapy of HIFU plus bufalin (HIFU+bufalin) is still uncertain. MATERIALS AND METHODS: A colony formation assay and flow cytometry were performed to measure the growth and induction of apoptosis in PC cells. Western blotting was used to explore the potential mechanism of HIFU and bufalin therapy. The in vivo efficacy of HIFU+bufalin was tested in a MiaPaCa2 xenograft model. RESULTS: Bufalin inhibited the growth of PC cells more obviously compared to HIFU. Combining bufalin with HIFU further decreased the growth of MiaPaCa2 cells compared with single therapy in vitro. Flow cytometry results showed that the percentage of surviving MiaPaCa2 cells in the bufalin-treated group and the HIFU-treated group was approximately three-fold and two-fold higher than in the HIFU+bufalin-treated group. Contrasting results were found in Panc-1 cells. Biochemical analysis revealed that HIFU+bufalin treatment elevated PARP expression and increased caspase-8 activation in MiaPaCa2 and Panc-1 cells. HIFU+bufalin significantly reduced the growth of MiaPaCa2 tumors compared with HIFU or bufalin treatment alone. HIFU+bufalin treatment decreased Ki67 staining and increased activated caspase-3 and caspase 8 staining, when compared with HIFU or bufalin treatment alone in mouse tumors. CONCLUSION: HIFU enhanced the effect of bufailn by inducing apoptosis in PC cells. A combination of HIFU and bufalin may be employed as an alternative therapeutic strategy for PC.

Jian Pi Li Qi Decoction Alleviated Postembolization Syndrome Following Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of Jian Pi Li Qi (JPLQ) decoction in improving quality of life of patients with hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE). METHODS: A randomized, double-blind, placebo-controlled trial was conducted. A total of 150 patients with HCC were randomly assigned into 3 groups. Groups were designed as follows: neither herbal medicine nor placebo administration (group A), placebo treatment (group B), and JPLQ decoction treatment (group C). The measurement methods of the observed outcomes include MD Anderson Symptom Inventory-Gastrointestinal module, armpit temperature, and laboratory tests. RESULTS: Among the 140 patients studied, the 12 symptoms rated as most severe, which characterize postembolization syndrome (PES), were fever, pain, fatigue, nausea, disturbed sleep, distress, lack of appetite, drowsiness, dry mouth, vomiting, constipation, and feeling bloated. All these increased significantly (all P < .05) after TACE; 7 symptoms, including fever, pain, fatigue, lack of appetite, drowsiness, dry mouth, and constipation (all P < .05), were found to be relieved significantly by JPLQ. JPLQ also improved the liver function damage caused by TACE. CONCLUSION: JPLQ decoction may be an effective modality to relieve PES and protect liver function in patients with HCC after TACE.

Effects and tolerance of silymarin (milk thistle) in chronic hepatitis C virus infection patients: a meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of silymarin on chronic hepatitis C virus- (HCV-) infected patients. METHODS: Randomized controlled trials (RCTs) of silymarin in chronic HCV-infected patients up to April 1, 2014 were systematically identified in PubMed, Ovid, Web of Science, and Cochrane Library databases. RESULTS: A total of 222 and 167 patients in five RCTs were randomly treated with silymarin (or intravenous silibinin) and placebo, respectively. Serum HCV RNA relatively decreased in patients treated with silymarin compared with those administered with placebo, but no significance was found (P = 0.09). Meta-analysis of patients orally treated with silymarin indicated that the changes of HCV RNA are similar in the two groups (P = 0.19). The effect on alanine aminotransferase (ALT) of oral silymarin is not different from that of placebo (P = 0.45). Improvements in quality-of-life (Short Form-36) in both silymarin and placebo recipients were impressive but relatively identical (P = 0.09). CONCLUSION: Silymarin is well tolerated in chronic HCV-infected patients. However, no evidence of salutary effects of oral silymarin has yet been reported based on intermediate endpoints (ALT and HCV RNA) in this population. Moreover, intravenous administration of silymarin should be further studied.

The preventive and therapeutic effect of acupuncture for radiation-induced xerostomia in patients with head and neck cancer: a systematic review.

BACKGROUND: Methods currently available to prevent and manage xerostomia which caused by radiotherapy in patients with head and neck caner have limited efficacy. Some studies suggest that acupuncture may be beneficial. OBJECTIVES: The authors evaluated the preventive and therapeutic effect of acupuncture for radiation-induced xerostomia among patients with head and neck cancer. METHODS: PUBMED, EMBASE, Cochrane Library, CBM, CAJD, Wan Fang database, and VIP Database for Chinese Technical Periodicals were electronically searched, in conjunction with further manual search for relevant articles. Studies that met the inclusion criteria were systematically evaluated. RESULTS: Three randomized controlled trials (RCTs) investigating the therapeutic effect of acupuncture were included. One RCT on the preventive effect of acupuncture was found. Because of the considerable variation among included studies, meta-analysis was not possible. Two included RCTs used placebo controls, and both observed significant improvement in the salivary flow rates between acupuncture and control groups. However, no significant differences were found. Three included RCTs suggested that acupuncture for radiation-induced xerostomia can improve patients' subjective symptoms. The only study evaluating the preventive effect of acupuncture for radiation-induced xerostomia showed positive changes in salivary flow rates (both unstimulated and stimulated) and dry mouth -related symptoms. Acupuncture treatment was well tolerated by all patients and no severe adverse effects were seen. CONCLUSIONS: Insufficient evidence is available to judge whether acupuncture is safe and whether it is effective in preventing or treating radiation-induced xerostomia. Significant research remains to be done before acupuncture can be recommended for routine use in radiation-induced xerostomia.