Hepatoblastoma (HB) is the most common hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Increasing evidence shows that dipeptidase 1 (DPEP1) has pivotal function in tumorigenesis in multiple tumors. However, the expression pattern, biological function, and underlying mechanism of DPEP1 in HB have not been reported. Here we showed that DPEP1 was significantly upregulated and was associated with poor prognosis in HB patients. In vitro and in vivo assays indicated that silencing DPEP1 significantly suppressed HB cell proliferation, migration, and invasion, while DPEP1 overexpression exhibited the opposite effect. In addition, we identified that DPEP1 was a direct target of microRNA-193a-5p (miR-193a-5p). Functional experiments demonstrated that overexpression of miR-193a-5p significantly inhibited cell proliferation and invasion of HB cells, while the inhibitory effect could be reversed by DPEP1 overexpression. Moreover, miR-193a-5p was decreased in HB tumor tissues and associated with a poor clinical prognosis. Mechanistically, our results indicated that the miR-193a-5p/DPEP1 axis participated to the progression of HB via regulating the PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin) signaling. In conclusion, our findings suggest that the miR-193a-5p /DPEP1 axis might be a good prognostic predictor and therapeutic target in HB.
Objective:This study was to review the efficacy of surgical resections in different clinical situations for a better understanding of the meaning of surgery in the treatment of neuroblastoma (NB).Data Sources:The online database ScienceDirect (2016–2018) was utilized. The search was conducted using the keywords “neuroblastoma,” “neuroblastoma resection,” “neuroblastoma surgery,” and “high-risk neuroblastoma.”Study Selection:We retrospectively analyzed of patients who underwent surgical resections in different clinical situations. The article included findings from selected relevant randomized controlled trials, systematic reviews, and meta-analyses or good-quality observational studies. Abstracts only, letters, and editorial notes were excluded. Full-text articles and abstracts were extracted and reviewed to identify key articles discussing surgery management of NB, which were then selected for critical analysis.Results:A total of 7800 English language articles were found containing references to NB (2016–2018). The 163 articles were searched which were related to the surgical treatment of NB (2016–2018). Through the analysis of these important articles, we found that the treatments of NB at low- and intermediate-risk groups were basically the same. High-risk patients remained controversial.Conclusions:NB prognosis varies tremendously based on the stage and biologic features of the tumor. After reviewing the relevant literature, patients with low-risk disease are often managed with surgical resection or observation alone with tumors likely to spontaneously regress that are not causing symptoms. Intermediate patients are treated with chemotherapy with the number of cycles depending on their response as well as surgical resection of the primary tumor. High-risk patients remain controversial. Multidisciplinary intensive treatment is essential, especially for patients who received subtotal tumor resection. Minimally invasive surgery for the treatment of NBs without image-defined risk factors in low- to high-risk patients is safe and feasible and does not compromise the treatment outcome. We conclude that ≥90% resection of the primary tumor is both feasible and safe in most patients with high-risk NB. New targeted therapies are crucial to improve survival.
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