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Background: Xanthoangelol (XAG) was reported to exhibit antitumor properties in several cancer. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC) and the relevant mechanisms are not known. Methods: The effects of XAG on HCC cell proliferation and apoptosis were respectively examined by CCK-8 assay and Annexin V-FITC/PI apoptosis kit. Western blotting was conducted to detect the expression of proteins. The effect of XAG on the development of acidic vesicle organelles was assessed using acridine orange staining. mRFP-GFP-LC3 adenovirus was used to transfect HCC cells and the formation of autolysosome was detected using a confocal microscope. Results: Mechanistically, XAG promotes HCC cell death through triggering intrinsic apoptosis pathway, not extrinsic apoptotic pathway. Furthermore, XAG treatment induced autophagy in Bel 7402 and SMMC 7721 cells, as evidenced by an increase in autophagy-associated proteins, including LC3B-II, Beclin-1, and Atg5. Interestingly, inhibition of autophagy with 3-MA, Bafilomycin A1 (Baf A1), or siRNA targeting Atg5 effectively enhanced the apoptotic cell ratio in XAG-treated cells, indicating that protective effect of autophagy induced by XAG in HCC. Moreover, autophagy induced by XAG was mediated by activating endoplasmic reticulum stress (ERS), along with administration of XAG, the expression levels of ERS-associated proteins, including CHOP, GRP78, ATF6, p-eIF2α, IRE1α, and cleaved caspase-12 were significantly increased in HCC cells. Meanwhile, suppressing ERS with chemical chaperones (TUDCA) or CHOP shRNA could effectively abrogate the autophagy-inducing effect of XAG, and increase the apoptotic cell death. Further mechanistic studies showed that ERS-induced autophagy in XAG-treated cells was mediated by activation of JNK/c-jun pathway. XAG treatment resulted in the increase of p-JNK and p-c-jun, while suppressing ERS with TUDCA or CHOP shRNA could effectively reverse it. Meanwhile, SP600125, a JNK inhibitor, effectively reversed XAG-induced protective autophagy and enhanced cell apoptosis in XAG-treated HCC cells. In vivo results demonstrated that XAG exerts potent antitumor properties with low toxicity. Conclusions: Collectively, these results suggested that XAG could be served as a promising candidate for the treatment and prevention of HCC. [ABSTRACT FROM AUTHOR]

Background: Dogs play a pivotal role in the transmission of cystic echinococcosis (CE), a zoonosis caused by the tapeworm Echinococcus granulosus. We showed previously that dogs vaccinated with two E. granulosus adult-worm specific proteins, EgM9 and EgM123, emulsified with Freund's adjuvants induced significant protective efficacy in terms of reduction in worm burden and egg production after 45 days post-infection. It was not known whether this protection can be sustained using adjuvants suitable for use in dogs. Methods: Recombinant EgM9 and EgM123 were mixed with Quil A or ISCOMs for vaccinating dogs. After three vaccine injections, all the dogs were orally challenge-infected with 200 000 protoscoleces of E. granulosus. After 45 days of infection, all the dogs were euthanized and necropsied for collecting and counting E. granulosus worms. Immunoglobins, including the IgG subclasses IgG1 and IgG2, were detected in the sera of vaccinated dogs by ELISA. To determine whether the protection efficacy could be maintained after 45 days post-infection, we implemented a longevity trial to count eggs in dog faeces for 170 days after infection. Results: The dogs vaccinated with EgM9 and EgM123 mixed with Quil A and ISCOMs showed similar protective efficacy as the proteins emulsified with Freund's adjuvants in our previous study in terms of reduction of worms and eggs at 45 days post-infection. The longevity trial showed that EgM9 protein-vaccinated group released lower number of eggs per gram compared with the egg counts in the control dogs during the dog trial study. Conclusion: EgM9 and EgM123 are thus suitable vaccine candidates against E. granulosus infection in dogs. [ABSTRACT FROM AUTHOR]

Background: In this study, a combination of recombinant adenoviral p53 (rAd-p53) gene therapy and intra-arterial delivery of chemotherapeutic agents for treatment of oral squamous cell carcinoma was evaluated.Methods: In total, 99 patients with stage III or IV oral carcinoma who had refused or were ineligible for surgery were enrolled in a randomized, placebo-controlled, double-blind, phase III clinical trial. They were randomly assigned to group I (n = 35; intra-arterial infusion of rAd-p53 plus chemotherapy), group II (n = 33; intra-arterial infusion of rAd-p53 plus placebo chemotherapy), or group III (n = 31; intra-arterial infusion of placebo rAd-p53 plus chemotherapy).Results: The median length of follow-up was 36 months (range, 3 to 86 months). During follow-up, 16 patients in group I, 20 in group II, and 22 in group III died. Group I (48.5%) had a higher complete response rate than groups II (16.7%) and III (17.2%) (P = 0.006). The rate of non-responders in group I was significantly lower than that in groups II and III (P < 0.020). A log-rank test for survival rate indicated that group I had a significantly higher survival rate than group III (P = 0.019). The survival rate of patients with stage III but not stage IV oral cancer was significantly higher in group I than in group III (P = 0.015, P = 0.200, respectively). The survival rate of patients with stage IV did not differ significantly among the three groups. Or the 99 patients, 63 patients experienced adverse events of either transient flu-like symptoms or bone marrow suppression, while 13 patients had both these conditions together. No replication-deficient virus was detected in patient serum, urine, or sputum. rAd-p53 treatment increased Bax expression in the primary tumor of 80% of patients, as shown by immunohistochemical staining.Conclusions: Intra-arterial infusion of combined rAd-p53 and chemotherapy significantly increased the survival rate of patients with stage III but not stage IV oral cancer, compared with intra-arterial chemotherapy. Intra-arterial infusion of combined rAd-p53 and chemotherapy may represent a promising alternative treatment for oral squamous cell carcinoma.Trial Registration: ChiCTR-TRC-09000392 (Date of registration: 2009-05-18). [ABSTRACT FROM AUTHOR]