NSUN2 is a RNA methyltransferase that has been shown to be implicated in development of human cancer. However, the functional role of NSUN2, mechanism of NSUN2 overexpression and its association with clinicopathologic features in breast cancer remain unclear. To investigate alterations in the expression and functional role of NSUN2 in breast cancer, NSUN2 expression was assessed in breast cancer cells and tissues obtained from cancers at different American Joint Committee on Cancer (AJCC) stages, and its functions were investigated using breast cancer cells. NSUN2 expression was shown to be significantly higher in breast cancer cells and tissues than in normal breast epithelial cells and tissues, at both mRNA and protein levels. Overexpression of NSUN2 was shown to promote cell proliferation, migration, and invasion while NSUN2 knockdown inhibited these processes in vitro and in vivo. NSUN2 expression level was associated with the methylation level of its promoter. Our results demonstrated that the overall expression of NSUN2 significantly correlated with clinical stage (P=0.027), tumor classification (P=0.012), pathological differentiation (P=0.023), as well as with the expression levels of estrogen receptor (P<0.001), progesterone receptor (P=0.001), and Ki-67 (P<0.001). Our findings provide a unique insight into the roles and effects of NSUN2 overexpression in breast cancer cells, and highlight the necessity of the investigation of novel therapeutic targets, such as NSUN2, for the improvement of breast cancer treatments.

BackgroundInterleukin 12 (IL-12) is a cytokine that has been reported to exhibit potent tumoricidal effects in animal tumor models. A combined approach using Paclitaxel and platinum-based doublet chemotherapy is the most commonly used backbone regimen for treating lung cancer. Despite numerous studies regarding the anti-tumor effects of IL-12 and the widespread use of conventional chemotherapy, few direct comparisons of IL-12 and conventional chemotherapy in the treatment of lung cancer have been performed.MethodsWe compared IL-12 to paclitaxel and cisplatin doublet chemotherapy in terms of efficacy against lung cancer in mouse models. The antitumor effect was measured by survival assays, histological analyses and imaging analyses. The cytokine levels were assessed using enzyme linked immunosorbent assay (ELISA) and flow cytometry (FACS). The spleen sizes were measured. CD31, CD105 and Vascular endothelial growth factor receptor 3 (VEGFR3) were analyzed using immunofluorescence. Matrix metalloprotein-9 (MMP-9) and cadherin 1 (CDH1) transcript levels were measured by quantitative PCR. Tumor cells apoptosis were examined by Tunel assay.ResultsThe results showed that IL-12 treatment inhibited lung tumor growth, resulting in the long-term survival of lung cancer-bearing mice. Further examination revealed that IL-12 rapidly activated NK cells to secrete IFN-γ, resulting in the inhibition of tumor angiogenesis. In contrast, paclitaxel and cisplatin doublet chemotherapy did not show the expected efficacy in orthotopic lung cancer models; the IFN-γ levels were not increased after this treatment, and the number of peripheral lymphocytes was reduced.ConclusionTogether, these animal model data indicate that IL-12 shows a better curative effect than PTX + CDDP doublet chemotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2701-7) contains supplementary material, which is available to authorized users.

Systemic lupus erythematosus (SLE) has protean clinical manifestations of varying severity over the course of its onset, exacerbation, remission and flare that could often pose significant challenges for clinicians in their decision making as to whether to treat aggressively or to look for concurrent conditions such as infection with opportunistic pathogens. Human cytomegalovirus (HCMV) is one of those pathogens and is frequently encountered in our daily management of lupus patients. To investigate the clinical characteristics and therapeutic options of active HCMV infection in patients with SLE, we retrospectively reviewed clinical data of 105 inpatients in our department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital (PUMCH) diagnosed with both SLE and active HCMV infection from January 2006 to January 2012. Three groups were designated that included 42 cases of HCMV triggering SLE, 31 cases of HCMV exacerbating SLE, and 32 cases of HCMV mimicking SLE flare based on the relationship of HCMV infection and SLE. 1) Hematocytopenia (81%), fever (73.3%) and liver dysfunction (54.3%) were the most common clinical manifestations. The differences among the three groups with regard to butterfly erythema, cutaneous vasculitis, arthritis, serositis, central nervous system involvement and renal involvement were statistically significant (p < 0.05). 2) Positive rate of HCMV-pp65, compared with HCMV-IgM and HCMV-DNA, was the highest (84.9%) in patients with SLE and active HCMV infection. 3) Following 14-21 days of inductive treatment with ganciclovir, a total of 26 out of 56 patients were still positive with HCMV-IgM (nine of 19, 47.6%) and pp65 (17/37, 45.9%). Among them, seven cases suffered HCMV relapses in three months with six cases of sustained HCMV-pp65 antigenemia. In conclusion, hematocytopenia, fever and liver dysfunction should remind us to consider HCMV infection. Butterfly erythema, cutaneous vasculitis, arthritis, serositis, central nervous system involvement and renal lesion were relatively characteristic symptoms of lupus activity. HCMV-pp65 is a sensitive indicator to guide antiviral therapy. Induction therapy using ganciclovir with a duration of 14∼21 days is not sufficient, and continued HCMV-pp65 positivity may require prolonged antiviral treatment in lupus patients.