Hepatoma is one of the most severe malignancies usually with poor prognosis, and many patients are insensitive to the existing therapeutic agents, including the drugs for chemotherapy and molecular targeted therapy. Currently, researchers are committed to developing the advanced formulations with controlled drug delivery to improve the efficacy of hepatoma therapy. Numerous inoculated, induced, and genetically engineered hepatoma rodent models are now available for formulation screening. However, animal models of hepatoma cannot accurately represent human hepatoma in terms of histological characteristics, metastatic pathways, and post-treatment responses. Therefore, advanced animal hepatoma models with comparable pathogenesis and pathological features are in urgent need in the further studies. Moreover, the development of nanomedicines has renewed hope for chemotherapy and molecular targeted therapy of advanced hepatoma. As one kind of advanced formulations, the polymer-based nanoformulated drugs have many advantages over the traditional ones, such as improved tumor selectivity and treatment efficacy, and reduced systemic side effects. In this article, the construction of rodent hepatoma model and much information about the current development of polymer nanomedicines were reviewed in order to provide a basis for the development of advanced formulations with clinical therapeutic potential for hepatoma.

In this study a cisplatin-loaded, multilayered polylactide (PLA) electrospun nanofibers, with the structure of two layers of drug-loaded mat being sandwiched by three layers of blank mat, were designed for prolonged cisplatin release at surgical margin to prevent local cancer recurrence following surgical resection in a murine model. In vivo drug release and biodistribution study suggested that the multilayered fibrous mat displayed a slower cisplatin release behavior and a more stable drug rentention in the local tissue within 24 h than that of single-layered fibrous mat. By covering the surgical site with the multilayered fibrous mat following resection of subcutaneous liver cancer in mice, retarded tumor recurrence, prolonged survival time and less systemic toxicity were observed compared with other treatment groups.

The mammalian target of rapamycin (mTOR) is dysregulated in diverse cancers and contributes to tumor progression and drug resistance. The first generation of mTOR inhibitors have failed to show clinical efficiency in treating pancreatic cancers due in part to the feedback relief of the insulin-like growth factor-1 receptor (IGF-1R)-AKT signaling pathway. The second generation of mTOR inhibitors, such as AZD8055, could inhibit AKT activation upon mTOR complex 2 (mTORC2) inhibition. However, whether this generation of mTOR inhibitors can obtain satisfactory activities in pancreatic cancer therapy remains unclear. In this study, we found AZD8055 did not show great improvement compared with everolimus, AZD8055 induced a temporal inhibition of AKT kinase activities and AKT was then rephosphorylated. Additionally, we found that AZD8055-induced transient AKT inhibition increased the expression and activation of epidermal growth factor receptor (EGFR) by releasing its transcriptional factors Fork-head box O 1/3a (FoxO1/3a), which might contribute to cell resistance to AZD8055. The in vitro and in vivo experiments further indicated the combination of AZD8055 and erlotinib synergistically inhibited the mTORC1/C2 signaling pathway, EGFR/AKT feedback activation, and cell growth, as well as suppressed the progression of pancreatic cancer in a xenograft model. This study provides a rationale and strategy for overcoming AZD8055 resistance by a combined treatment with the EGFR inhibitor erlotinib in pancreatic cancer therapy.

Extrahepatic cholangiocarcinoma (EHCC) is a refractory malignancy with poor prognosis due to its early invasion, metastasis and recurrence after operation. Therefore, understanding the mechanisms of invasion and metastasis is the key to the development of new and effective therapeutic strategies for EHCC. In the present study we demonstrated that miR-221 promoted EHCC invasion and metastasis through targeting PTEN and formed a positive feedback loop with β-catenin/c-Jun signaling pathway. We found miR-221 was upregulated in EHCC specimens and CC cell lines. Moreover, miR-221 was found strongly associated with the metastasis and prognosis of EHCC patients. The expression of PTEN was downregulated in EHCC patients and CC cell lines, and was further demonstrated as one of the downstream targets of miR-221. In addition, our data indicated that β-catenin activated miR-221 through c-jun, while miR-221 enhanced β-catenin signaling induced-epithelial-mesenchymal transition (EMT) by targeting PTEN, hence forming a positive feedback loop in EHCC cell lines. In conclusion, our results suggested that miR-221 promotes EMT through targeting PTEN and forms a positive feedback loop with β-catenin/c-Jun signaling pathway in EHCC.

The study aimed to investigate the risk factors of postpancreatectomy hemorrhage (PPH) after pancreaticoduodenectomy (PD). A retrospective analysis of 423 patients who underwent PD between January 2008 and January 2014 was conducted. The overall incidence and all-cause mortality of PPH were 9.9% (42/423) and 2.1% (9/423), respectively. Independent risk factors of early PPH were revascularization (odds ratio (OR) = 6.786; 95% confidence interval (95% CI): 1.785–25.792; P=0.005), history of abdominal surgery (OR = 5.009; 95% CI: 1.968–12.749; P=0.001), and preoperative albumin levels (OR = 4.863; 95% CI: 1.962–12.005; P=0.001). Independent risk factors of late PPH included postoperative pancreatic leakage (OR = 4.696; 95% CI: 1.605–13.740; P=0.005), postoperative biliary fistula (OR = 6.096; 95% CI: 1.575–23.598; P=0.009), postoperative abdominal infection (OR = 4.605; 95% CI: 1.108–19.144; P=0.036), revascularization (OR = 9.943; 95% CI: 1.900–52.042; P=0.007), history of abdominal surgery (OR = 8.790; 95% CI: 2.779–27.806; P<0.001), and preoperative albumin levels (OR = 5.563; 95% CI: 1.845–16.776; P=0.002).