BackgroundGlioblastoma multiforme (GBM) is the most common primary central nervous system neoplasm in adults. Radioactive 125I seed implantation has been widely applied in the treatment of cancers. Moreover, previous clinical trials have confirmed that 125I seeds treatment was an effective therapy in GBM. We sought to investigate the effect of 125I seed on GBM cell growth and Epithelial-mesenchymal transition (EMT).MethodsCells were exposed to irradiation at different doses. Colony-formation assay, EdU assay, cell cycle analysis, and TUNEL assay were preformed to investigate the radiation sensitivity. The effects of 125I seeds irradiation on EMT were measured by transwell, Boyden and wound-healing assays. The levels of reactive oxygen species (ROS) were measured by DCF-DA assay. Moreover, the radiation sensitivity and EMT were investigated with or without pretreatment with glutathione. Additionally, nude mice with tumors were measured after treated with radiation.ResultsRadioactive 125I seeds are more effective than X-ray irradiation in inhibiting GBM cell growth. Moreover, EMT was effectively inhibited by 125I seed irradiation. A mechanism study indicated that GBM cell growth and EMT inhibition were induced by 125I seeds with the involvement of a ROS-mediated signaling pathway.ConclusionsRadioactive 125I seeds exhibit novel anticancer activity via a ROS-mediated signaling pathway. These findings have clinical implications for the treatment of patients with GBM by 125I seeds.

Background:Intensity-modulated radiotherapy (IMRT) is the main salvage treatment for advanced locally recurrent nasopharyngeal carcinoma (NPC); however, survival outcomes vary. We aimed to construct a prognostic-score model to identify patients who could benefit from salvage IMRT.Methods:This retrospective study involved 251 patients with locally recurrent NPC. The following parameters were analysed following IMRT: patient performance status, age, gender, late complications, T-stage of recurrence, synchronous nodal recurrence, primary gross tumour volume (GTV-nx), disease-free interval, re-irradiation dose and chemotherapy. The model was based on the hazard ratio coefficients of six significantly negative prognostic factors for survival.Results:Significantly negative prognostic factors included Karnofsky Performance Status ⩽70, age >50 years, late complications, recurrent T3–4 stage, synchronous nodal recurrence and GTV-nx >30 cm3. Three subgroups were defined according to model scores: low risk (0–4), intermediate risk (5–8) and high risk (9–15). The 5-year overall survival rates were 64.3%, 32.2% and 7.7%, respectively. The main cause of death was radiation-induced complications.Conclusion:The prognostic-score model demonstrated that re-irradiation with IMRT is suitable for low-risk and intermediate-risk patients but may be unsuitable for high-risk patients. Further research into the protection of critical adjacent organs to reduce late complications in these patients is warranted.

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Junctional adhesion molecule-A (JAM-A) is preferentially concentrated at tight junctions and influences epithelial cell morphology and migration. Epithelial-to-mesenchymal transition (EMT) is the conversion process of epithelial cells into mesenchymal cells, and it plays an important role in the invasiveness and metastasis of various cancers. However, the role of JAM-A in regulating the invasive behaviours of human nasopharyngeal carcinoma (NPC) is unknown. In this study, we found that JAM-A upregulation induced EMT, whereas silencing of endogenous JAM-A expression reversed EMT. Furthermore, upregulation of JAM-A led to EMT via activation phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. PI3K inhibitors blocked JAM-A-induced EMT, suggesting that the kinase acts downstream of JAM-A. Finally, results from 172 human patients with NPC showed that high expression levels of JAM-A correlated with metastasis and poor prognosis in NPC. Taken together, these results suggest that high JAM-A expression positively correlates with poor prognosis in patients with NPC, and induces EMT of NPC cells in vitro and in vivo via the PI3K/Akt pathway. These data indicate novel functions in the JAM-A repertoire, and have clinical implications for the treatment of patients with NPC.

Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.

Background: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these agents in the treatment of ALK positive NSCLC.Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib. PFS was the primary outcome while other outcomes like ORR, adverse events, quality of life and OS were also analyzed and compared. Hazard ratios and odds ratios obtained were analyzed using fixed effect or random effects model in Review Manager Software.Results: A total of 12 studies (n = 3,297) met the criteria for inclusion in this review and meta-analysis. ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings. Intracranial response rate was better with ALK inhibitors (ceritinib and alectinib) as compared to chemotherapy OR 6.51 [2.86, 14.83; p < 0.00001]. No significant increase in grade 3 or 4 adverse events was observed with crizotinib (OR 1.21 [0.82, 1.77; p = 0.34]) or ceritinib (OR 1.49 [0.86, 2.57; p = 0.17]) when compared to chemotherapy individually. Quality of life indicators assessed were significantly improved with ALK inhibitors. Next generation agents (ceritinib, alectinib and brigatinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.57; p < 0.00001]), ORR (OR 1.57 [1.21, 2.04; p = 0.0006]) in comparison to crizotinib. Next generation agents (Alectinib and brigatinib) yielded better response intra-cranially than crizotinib in terms of objective response rate (OR 5.87 [3.49, 9.87; p < 0.00001]) and time to CNS progression (HR 0.25 [0.13, 0.46; p < 0.0001]). Alectinib by far resulted in fewer adverse events than chemotherapy or crizotinib.Conclusions: Overall ALK inhibitors are safe and effective treatment option in ALK+ non-small cell lung cancer. Of the ALK inhibitors, Next generation agents in particular alectinib and brigatinib are safer and more effective intra-cranially and can be preferred as first option.

Although radiotherapy technology has progressed rapidly in the past decade, the inefficiency of radiation and cancer cell resistance mean that the 5-year survival rate of patients with nasopharyngeal carcinoma (NPC) is low. Radioactive 125I seed implantation has received increasing attention as a clinical treatment for cancers. Vascular endothelial growth factor-A (VEGF-A) is one of the most important members of the VEGF family and plays an important role in cell migration through the extracellular-signal-regulated kinase (ERK) pathway. Here we show that radioactive 125I seeds more effectively inhibit NPC cell growth through DNA damage and subsequent induction of apoptosis, compared with X-ray irradiation. Moreover, cell migration was effectively inhibited by 125I seed irradiation through VEGF-A/ERK inactivation. VEGF-A pretreatment significantly blocked 125I seed irradiation-induced inhibition of cell migration by recovering the levels of phosphorylated ERK (p-ERK) protein. Interestingly, in vivo study results confirmed that 125I seed irradiation was more effective in inhibiting tumor growth than X-ray irradiation. Taken together, these results suggest that radioactive 125I seeds exert novel anticancer activity by triggering DNA damage and inactivating VEGF-A/ERK signaling. Our finding provides evidence for the efficacy of 125I seeds for treating NPC patients, especially those with local recurrence.

BackgroundAccurate and early prognosis of disease is essential to clinical decision making, particularly in diseases, such as HCC, that are typically diagnosed at a late stage in the course of disease and therefore carry a poor prognosis. CDCA5 is a cell cycle regulatory protein that has shown prognostic value in several cancers.MethodsWe retrospectively evaluated 178 patients with HCC treated with curative liver resection between September 2009 and September 2012 at Nanchong Central Hospital in Nanchong, Sichuan Province, China. Patients were screened for their CDCA5 expression levels and assigned to either the high or low expression group. Patient demographics, comorbidities, clinicopathologic data, such as tumor microvascular invasion status and size, and long-term outcomes were compared between the two groups. The effect of CDCA5 on the proliferation of liver cancer cells was analyzed using in vitro and in vivo assays.ResultsThe present study found that increased CDCA5 expression was associated with increased tumor diameter and microvascular invasion in HCC. It was also found that CDCA5 overexpression may be associated with liver cancer cells. Additionally, this study confirmed that CDCA5 expression was increased in HCC tissue versus normal liver tissue, that CDCA5 expression was associated with decreased survival and that CDCA5 knockdown using shRNA led to cell cycle arrest in the G2/M phase.ConclusionsThese findings suggest that CDCA5 expression is associated with poor prognosis in patients with hepatocellular carcinoma.