The immune-chemo-embolization effect of temperature sensitive gold nanomedicines against liver cancer

Although transcatheter arterial chemo-embolization(TACE)plays a key role on clinical treatment of hepatocellular carcinoma(HCC),it was greatly limited by the poor synergistic effect between chemotherapeutics and physical embolization to tumor-feeding arteries.In the present work,a temperature sensitive polymer poly(N-isopropylacrylamide-b-methacrylic acid)(PNA),which was modified with gold nanoparticles(AuNP@PNA),was successfully used to encapsulate doxorubicin(DOX)by electrostatic binding with their carboxyl groups.The resultant gold nanomedicines(AuNP@PNA/DOX)exhibited temperature responsive sol-gel phase transition,favorable shear thinning effect and X-ray angiography.By in vivo evaluation of vascular embolization on VX2-tumor-bearing rabbits,AuNP@PNA/DOX exhibited far better antitumor efficacy than Lipiodol/DOX,on either tumor growth inhibition,proliferation,apoptosis,necrosis or anti-metastasis.Owing to sufficient embolization to tumor vascular networks,AuNP@PNA/DOX down-regulated the expression levels of HIF-1α,VEGF and MMP-9,and prompted more efficient activation on CD3+/CD8+T cells and the related cytokines,suggesting the synergistic effect between AuNP@PNA and DOX on the improvement of post-operative tumor immunosuppressive microenvironment.With their favorable pharmcokinetics and biocompatibility,AuNP@PNA/DOX is promising to be developed as a multi-functional artery-imaging/embolic agent with immune-chemo-embolization for enhancing TACE efficacy on HCC.

Locoregional therapy response in patients with hepatocellular cancer waiting for liver transplantation:Only selection or biological effect?

Locoregional treatments(LRT) represent a broad strategy used for reducing the risk of drop-off and contextually improving the survivals in patients with hepatocellular cancer receiving a liver transplantation(LT). However, it is not sufficiently clear if LRT are only a surrogate of tumor aggressiveness or if they consent a real benefit in terms of tumor stabilization. A recent study by Pommergaard et al reported the results from the European Liver Transplant Registry. Patients receiving LRT before LT had better 5-year survival rates respect to no-LRT cases(69.7% vs 65.8%; P < 0.001). When the number of LRT was tested, one-to-two treatments were connected with improved survivals respect to no treatment [hazard ratio(HR) = 0.85 and 0.71, respectively]. The efficacy of LRT was also reported in the presence of larger tumors(HR = 0.78) and micro-macrovascular invasion(HR = 0.71). The results observed in the present study are partially in discordance with other analyses showing a detrimental effect of LRT. The main problem in the interpretation of these results is connected with the possible initial selection biases present in the studies. The most recent guidelines suggest to perform LRT before the transplant, but the level of evidence is typically low due to the absence of prospectively designed studies.

Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common cause of liver malignancy and the fourth leading cause of cancer deaths universally.Cure can be achieved for early stage HCC,which is defined as 3 or fewer lesions less than or equal to 3 cm in the setting of Child-Pugh A or B and an ECOG of 0.Patients outside of these criteria who can be down-staged with loco-regional therapies to resection or liver transplantation(LT)also achieve curative outcomes.Traditionally,surgical resection,LT,and ablation are considered curative therapies for early HCC.However,results from recently conducted LEGACY study and DOSISPHERE trial demonstrate that transarterial radio-embolization has curative outcomes for early HCC,leading to its recent incorporation into the Barcelona clinic liver criteria guidelines for early HCC.This review is based on current evidence for curativeintent loco-regional therapies including radioembolization for early-stage HCC.