Bromodomain containing 7 (BRD7) was identified as a nuclear transcriptional regulatory factor. BRD7 functions as a tumor suppressor in multiple cancers, including nasopharyngeal carcinoma (NPC). In this study, we reported a novel mechanism of BRD7 in NPC progression. We demonstrated that the expression of miR-141 was remarkably increased in NPC tissues and was negatively correlated with the expression of BRD7 and the survival rate of NPC patients. Decreased expression levels of miR-141, including the primary, the precursor and the mature forms of miR-141, were found in BRD7-overexpressing HEK293, 5-8F and HNE1 cells compared the control cells, while there was no obvious effect on the expression levels of the two critical enzymes Drosha and Dicer. BRD7 can negatively regulate the promoter activity of miR-141, while no obvious binding site of BRD7 was found in the potential promoter region of miR-141. Moreover, ectopic expression of miR-141 can significantly promote cell proliferation and inhibit apoptosis in NPC, and rescuing the expression of miR-141 in BRD7-overexpressing NPC cells could partially reverse the tumor suppressive effect of BRD7 on cell proliferation and tumor growth in vitro and in vivo. Furthermore, the activation of the PTEN/AKT pathway mediated by the overexpression of BRD7 could be inhibited by rescuing the expression of miR-141, which accordingly results in the partial restoration of cell proliferation and tumor growth. Our findings demonstrate that the BRD7/miR-141/PTEN/AKT axis has critical roles in the progression of NPC and provide some promising targets for the diagnosis and treatment of NPC.
Highly porous (70%) and large pore sized Ti-Al alloys with low thermal conductivity were successfully fabricated by reactive infiltration of Al in porous Ti preform. The porousTi-Al alloy has a single phase structure of c-TiAl, and the average pore size is y100 mm. The formation mechanism of the porous structure was discussed. The thermal conductivity was determined by the laser flash method, and the effect of porosity on the thermal conductivity was studied. The thermal conductivity of the porous Ti-Al alloy is about 1/3 of the bulk alloy. The results show that the porous Ti-Al alloys have good bending strength.
In consideration of the results of the RTOG0617 study, researchers began to adopt a prudent policy to high-dose radiotherapy. Based on the assume that radiation dose escalation to the primary tumor can improve local control and therefore producing survival benefits under the condition of limiting the dose to the organ at risk (OAR), we launched the study to evaluate the effect of simultaneous Integrated boost (SIB) radiotherapy implemented on the stage III local-advanced non-small cell lung cancer (LA-NSCLC) patients. Materials/Methods: 42 Patients with stage III LA-NSCLC who were eligible for definite concurrent chemoradiotherapy were prospectively given the radiation regimen of single dose of 2.0Gy for PTV, 2.2Gy for CTV, and 2.4 -2.8Gy for GTV with 25 fractions. Other stage III LA-NSCLC patients retrospectively collected with routinely radiotherapy were matched through PSM. 2 Cycles of platinum based concurrent chemotherapy were carried on patients in both groups. The primary endpoints were progression-free survival (PFS), toxic effects and dose for normal tissues, with the secondary end point of overall survival (OS). The Kaplan-Meier method was used to evaluate PFS and OS, and the Mann-Whitney U test for toxic effects and the dose for normal tissues. Results: The median PFS time was 20.6 vs 9.0 months (P = 0.01), and the median OS was 40.0 vs 24.5 months (P = 0.02) in the SIB group and the control group respectively, all were obviously longer in the SIB group. No significant differences of radiation-related pneumonitis (P = 0.95) and myelosuppression (P = 0.40) have been observed between the two groups, as well as nausea, vomiting, esophagitis and dyspnea. The dose and the radiation-effected volume to the surrounding normal tissues also did not show the tendency of increasement in the SIB group. Conclusion:The results of our research has revealed that the dose escalation did improve the PFS and OS while not increased the dose to the surrounding normal tissues and the occurrence of toxic effects. Simultaneous integrated boost radiotherapy to the primary tumor might be a safe and feasible regimen to improve survival benefit for the stage III LA-NSCLC patients eligible for definite concurrent chemoradiotherapy in the future.
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