BackgroundHOTAIR was known to enhance radioresistance in several cancers. However, the function of HOTAIR on radioresistance involving the regulation of HIF-1α in cervical cancer has not been reported.MethodsBALB/c nude mice were injected subcutaneously with HeLa cells and irradiated by X-ray. The tumor volume was measured and the expression of HOTAIR in tumors was detected by quantitative real-time PCR. Western blot was performed to detect the protein level of HIF-1α. MTT (3-(4,5-Dimethylthiazol-2-yl) 22,5-diphenyltetrazolium bromide) assay and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to examine the cell viability and cell apoptosis of HeLa cells and C33A cells exposed to radiation.ResultsRadiotherapy inhibited the tumor growth in mice bearing HeLa cells. Radiotherapy reduced the expression of HOTAIR and HIF-1α in tumor tissues and HeLa cells or C33A cells. HOTAIR overexpression abrogated the effect of radiation on the cell viability and cell apoptosis of HeLa and C33A cells. HOTAIR also upregulated the expression of HIF-1α in HeLa and C33A cell exposed to radiation. HIF-1α knockdown reversed increasing cell viability and reducing apoptosis of HeLa and C33A cell induced by HOTAIR overexpression. HOTAIR overexpression promoted tumor growth in mice bearing HeLa and exposed to radiation.ConclusionRadiotherapy might inhibit cervical cancer cell growth through HOTAIR/HIF-1α pathway.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1153-4) contains supplementary material, which is available to authorized users.

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ObjectivesThe anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour actively in models of HER2-positive breast cancer. However, the efficacy of trastuzumab in combination with lapatinib remains controversial. Therefore, we conducted this meta-analysis to compare combination treatment with lapatinib and trastuzumab to trastuzumab or lapatinib alone in the treatment of HER2-positive breast cancer.MethodsRandomised controlled trials (RCTs), published in PubMed, Embase and Web of Science, were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with breast cancer who were treated with lapatinib and trastuzumab. Outcomes included pathological complete response (pCR), event-free survival (EFS), overall survival (OS) and toxicities. Results were expressed as the risk ratio (RR) or HR with 95% CIs. Pooled estimates were calculated by using a fixed-effects model or a randomised-effects model.ResultsA total of 7 RCTs involving 2084 patients met the inclusion criteria and were included in this meta-analysis. The combination of lapatinib and trastuzumab significantly improved pCR (RR=1.43, 95% CI 1.23 to 1.67; p<0.001), EFS (HR=0.75, 95% CI 0.60 to 0.93; p=0.009) and OS (HR=0.72, 95% CI 0.56 to 0.93; p=0.011) in the treatment of HER2-positive breast cancer compared with trastuzumab or lapatinib alone. The combination treatment also increased the pCR irrespective of hormone receptor status and tumour size. More frequent grade 3 or 4 adverse events, including diarrhoea, rash or erythema, neutropenia and hepatic adverse events, were found in the combination group than in the trastuzumab or lapatinib group.ConclusionsOn the basis of the current evidence, our results reveal that the addition of lapatinib to trastuzumab can significantly improve pCR, EFS and OS with a tolerated toxicity in patients with HER2-positive breast cancer. Further well-conducted, large-scale trials are needed to validate these findings.

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To guarantee the smooth operation of trains, rail grinding and wheel turning are necessary practices to remove surface defects. Surface integrity of machined wheel/rail materials is significant to affect their tribological performance. In this paper, firstly, the wheel specimens were turned by a CNC lathe and the rail specimens were ground by a cylindrical grinding machine with various machining parameters. Then, the wear and damage behavior of the machined wheel/rail discs was systematically investigated via a twin-disc wear testing apparatus under dry rolling-sliding condition. The experimental results show that the surface hardness of rail discs after machining is slightly higher than that of wheel discs, while the surface roughness and plastic deformation layer of wheel discs are much larger than those of rail discs. The surface hardness increase degree of rail discs and their thickness of plastic deformation layer are greater than those of wheel discs after the rolling-sliding test. The wear loss of wheel discs is much larger than that of rail discs. Surface roughness, hardness and plastic deformation layer of wheel/rail discs after machining exert a comprehensive effect on the wear behavior, and friction pair with appropriate original surface hardness and roughness generates the smallest amount of wear loss.