Hepatic alveolar echinococcosis (HAE) is a zoonotic parasitic disease caused by the larvae of Echinococcus multilocularis. Because of its characteristics of diffuse infiltration and growth similar to tumors, the disability rate and mortality rate are high among patients. Although surgery (including hepatectomy, liver transplantation, and autologous liver transplantation) is the first choice for the treatment of hepatic alveolar echinococcosis in clinic, drug treatment still plays an important and irreplaceable role in patients with end-stage echinococcosis, including patients with multiple organ metastasis, patients with inferior vena cava invasion, or patients with surgical contraindications, etc. However, Albendazole is the only recommended clinical drug which could exhibit a parasitostatic rather than a parasitocidal effect. Novel drugs are needed but few investment was made in the field because the rarity of the cases. Drug repurposing might be a solution. In this review, FDA-approved drugs that have a potential curative effect on hepatic alveolar echinococcosis in animal models are summarized. Further, nano drug delivery systems boosting the therapeutic effect on hepatic alveolar echinococcosis are also reviewed. Taken together, these might contribute to the development of novel strategy for advanced hepatic alveolar echinococcosis.
Opposite roles of circular RNA MM-associated circular RNA (circ-MYBL2) have been observed in different malignancies, and its role in pancreatic adenocarcinoma (PA) is unknown. Our preliminary sequencing data revealed its inverse correlation with microRNA-19a (miR-19a). This study was performed to explore the role of circ-MYBL2 in PA and its crosstalk with miR-19a. The accumulation of circ-MYBL2 and miR-19a in PA was detected by RT-qPCR. Participation of circ-MYBL2 in the regulation of miR-19a and its RNA gene methylation was studied with an overexpression assay, followed by RT-qPCR and MSP analyses. The role of miR-19a and circ-MYBL2 in PA cell proliferation and movement was evaluated using the BrdU assay and the Transwell assay, respectively. Downregulation of circ-MYBL2 and upregulation of miR-19a were observed in PA. In PA cells, circ-MYBL2 decreased the accumulation of miR-19a but increased its RNA gene methylation. Overexpression of circ-MYBL2 decreased PA cell proliferation and movement, while overexpression of miR-19a showed an opposite effect. In addition, circ-MYBL2 suppressed the role of miR-19a in cell proliferation, migration, and invasion. In conclusion, circ-MYBL2 was downregulated in PA and it downregulated miR-19a through methylation to suppress PA cell proliferation.
Immune checkpoint inhibitor (ICI) is one of the most important tumor treatment methods. Although the therapeutic efficiency of immune checkpoint inhibitor mono-therapy is limited, the combination of chemotherapy plus immune checkpoint inhibitors has shown great advantages in cancer treatment. This is mainly due to the fact that tumor reactive T cells could fully provide their anti-tumor function as chemotherapy could not only cause immunogenic cell death to increase antigen presentation, but also improve the immunosuppressive tumor micro-environment to synergize with immune checkpoint inhibitors. However, traditional chemotherapy still has shortcomings such as insufficient drug concentration in tumor region, short drug duration, drug resistance, major adverse events, etc, which might lead to the failure of the therapy. Nano chemotherapeutic drugs, which refer to chemotherapeutic drugs loaded in nano-based drug delivery system, could overcome the above shortcomings of traditional chemotherapeutic drugs to further improve the therapeutic effect of immune checkpoint inhibitors on tumors. Therefore, the scheme of nano chemotherapeutic drugs combined with immune checkpoint inhibitors might lead to improved outcome of cancer patients compared with the scheme of traditional chemotherapy combined with immune checkpoint inhibitors.
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