52 research outputs found

    Search for standard model production of four top quarks in the lepton + jets channel in pp collisions at √s = 8 TeV

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    Open Access, Copyright CERN, for the benefit of the CMS Collaboration. Article funded by SCOAP3.Abstract: A search is presented for standard model (SM) production of four top quarks (Formula presented.) in pp collisions in the lepton + jets channel. The data correspond to an integrated luminosity of 19.6 fb−1 recorded at a centre-of-mass energy of 8 TeV with the CMS detector at the CERN LHC. The expected cross section for SM (Formula presented.) production is (Formula presented.). A combination of kinematic reconstruction and multivariate techniques is used to distinguish between the small signal and large background. The data are consistent with expectations of the SM, and an upper limit of 32 fb is set at a 95% confidence level on the cross section for producing four top quarks in the SM, where a limit of 32 ± 17 fb is expected

    The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

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    AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

    Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.

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    Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern of stem cell (SC) markers during tumor development. In this study, we were interested to identify SC genes methylation profiles during cervical carcinogenesis. A genome-wide promoter methylation screening revealed a strong hypermethylation of Undifferentiated cell Transcription Factor 1 (UTF1) promoter in cervical cancer in comparison with normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid-based cytological samples, we showed that UTF1 promoter methylation increases with lesion severity, the highest level of methylation being found in carcinoma. This hypermethylation was associated with increased UTF1 mRNA and protein expression. By using quantitative RT-PCR and Western Blot, we showed that both UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the absence of its two main described regulators Oct4A and Sox2. Moreover, by immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines. Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine was associated with decreased UTF1 gene methylation and expression in two cervical cancer cell lines of the four tested. These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis and raise the questions of its role during epithelial carcinogenesis and of the mechanisms regulating its expression

    <i>UTF1</i> expression increases during cervical carcinogenesis.

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    <p>A) Expression of <i>UTF1</i> mRNA in liquid-based cytological samples. Expression was assessed by quantitative RT-PCR. Ecto, normal ectocervix; LSIL, low grade squamous intraepithelial lesion; HSIL, high grade squamous intraepithelial lesion; SCC, squamous cell carcinoma. B) Immunohistochemical staining of UTF1 protein in cervical tissue samples, magnification ×200. C) semi-quantitative analysis of staining. Testis, positive control; Neg, negative control without primary antibody. *, <i>p</i><0.05; **, <i>p</i><0.01 (Kruskal-Wallis followed by Dunn's Multiple Comparison test).</p

    <i>UTF1</i> promoter methylation analysis by direct bisulfite pyrosequencing in white blood cells.

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    <p>Mean methylation value for each CpG analysed by direct bisulfite pyrosequencing in DNA from white blood cells. Position of each CpG is indicated (TSS = +1). The mean methylation values for HSIL and SCC in LBC samples were added as a comparison. WBC, white blood cells.</p

    Expression of <i>UTF1</i> and its regulators <i>Oct4A</i> and <i>Sox2</i> in cervical cancer cell lines.

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    <p>A) Quantitative RT-PCR. B) Western Blot. C) Immunofluorescence; magnification ×400. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042704#s3" target="_blank">Results</a> are representative of 3 independent experiments. *, <i>p</i><0.05 <i>vs</i> NCCIT+RA; ***, <i>p</i><0.001 <i>vs</i> NCCIT+RA (Unpaired t test).</p

    Effect of 5-aza on cell proliferation and viability.

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    <p>A) Cell proliferation. Cells were counted every 24 hrs during treatment with 5-AZA. B) Cell viability was measured with MTT test. **, p<0,01; ***, p<0,005 (Mann-Whitney U-Test). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042704#s3" target="_blank">Results</a> are representative of 3 independent experiments.</p
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