393 research outputs found

    Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

    Get PDF
    BACKGROUND: Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma. METHODS: We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters. RESULTS: HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome. CONCLUSION: HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential

    Induction of endogenous Îł-globin gene expression with decoy oligonucleotide targeting Oct-1 transcription factor consensus sequence

    Get PDF
    Human ÎČ-globin disorders are relatively common genetic diseases cause by mutations in the ÎČ-globin gene. Increasing the expression of the Îł-globin gene has great benefits in reducing complications associated with these diseases. The Oct-1 transcription factor is involved in the transcriptional regulation of the Îł-globin gene. The human Îł-globin genes (both AÎł and GÎł-globin genes) carry three Oct-1 transcription factor consensus sequences within their promoter regions. We have studied the possibility of inducing Îł-globin gene expression using decoy oligonucleotides that target the Oct-1 transcription factor consensus sequence. A double-stranded 22 bp decoy oligonucleotide containing the Oct-1 consensus sequence was synthesized. The results obtained from our in vitro binding assay revealed a strong competitive binding of the decoy oligonucleotide for the Oct-1 transcription factor. When K562 human erythroleukemia cells were treated with the Oct-1 decoy oligonucleotide, significant increases in the level of the Îł-globin mRNA were observed. The results of our western blots further demonstrated significant increases of the fetal hemoglobin (HbF, α2Îł2) in the Oct-1 decoy oligonucleotide-treated K562 cells. The results of our immunoprecipitation (IP) studies revealed that the treatment of K562 cells with the Oct-1 decoy oligonucleotide significantly reduced the level of the endogenous Îł-globin gene promoter region DNA co-precipitated with the Oct-1 transcription factor. These results suggest that the decoy oligonucleotide designed for the Oct-1 transcription factor consensus sequence could induce expression of the endogenous Îł-globin gene through competitive binding of the Oct-1 transcription factor, resulting in activation of the Îł-globin genes. Therefore, disrupting the bindings of the Oct-1 transcriptional factors with the decoy oligonucleotide provides a novel approach for inducing expression of the Îł-globin genes. It also provides an innovative strategy for the treatment of many disease conditions, including sickle cell anemia and ÎČ-thalassemia

    c-erbB-2 is not a major factor in the development of colorectal cancer

    Get PDF
    We have investigated c-erbB-2 protein expression in a large cohort of well-characterized colorectal tumours, and in a subset of lymph node metastases. We have also evaluated a Val655Ile single nucleotide polymorphism, which is associated with an increased risk of breast cancer, in a subset of the colorectal cancer patients and in healthy control subjects. Immunohistochemical studies revealed that while 81.8% of tumours expressed c-erbB-2, in the majority of cases equivalent levels of c-erb-B2 were seen in adjacent normal mucosa. Colon tumours were significantly more likely to express c-erbB-2 than rectal tumours (P=0.015). Only 52.4% of the metastases displayed staining patterns concordant with their primary tumour, indicating that determination of c-erbB-2 protein in colorectal tumours cannot predict the status of lymph node metastases. PCR–RFLP analysis of the Val655Ile single nucleotide polymorphism demonstrated that allele frequencies were identical between colorectal cancer patients and a control group of Caucasian subjects (Ile=0.80 and Val=0.20 in each case), indicating that it is not related to the risk of developing colorectal cancer in this population. Furthermore, there was no relationship between c-erbB-2 protein expression and gene polymorphism (P=0.58). In terms of prognosis, no association was seen between either c-erbB-2 protein expression or the presence of the Val allele and patient survival (P>0.05 in each case), suggesting that c-erbB-2 is not a prognostic marker in colorectal cancer

    ヹォăƒȘăƒ§ă‚Żă‚żă‚€ă‚Źă‚żă€€ăƒ•ă‚§ăƒŹăƒ‰ă‚­ă‚·ăƒłă€€ăƒŽă€€ă‚łă‚Šă‚Ÿă‚Šă€€ă‚«ă‚€ă‚»ă‚­ă€€2.8â„«ă€€ăƒ–ăƒłă‚«ă‚€ăƒŽă‚Š

    Get PDF
    Remarkable progress in the physical parameters of net-current free plasmas has been made in the Large Helical Device (LHD) since the last Fusion Energy Conference in Chengdu, 2006 (O.Motojima et al., Nucl. Fusion 47 (2007) S668). The beta value reached 5 % and a high beta state beyond 4.5% from the diamagnetic measurement has been maintained for longer than 100 times the energy confinement time. The density and temperature regimes also have been extended. The central density has exceeded 1.0 x 10^21 m^-3 due to the formation of an Internal Diffusion Barrier (IDB). The ion temperature has reached 6.8 keV at the density of 2 x 10^19m^-3, which is associated with the suppression of ion heat conduction loss. Although these parameters have been obtained in separated discharges, each fusion-reactor relevant parameter has elucidated the potential of net-current free heliotron plasmas. Diversified studies in recent LHD experiments are reviewed in this paper

    Epigenetic regulation of mucin genes in human cancers

    Get PDF
    Mucins are high molecular weight glycoproteins that play important roles in diagnostic and prognostic prediction and in carcinogenesis and tumor invasion. Regulation of expression of mucin genes has been studied extensively, and signaling pathways, transcriptional regulators, and epigenetic modification in promoter regions have been described. Detection of the epigenetic status of cancer-related mucin genes is important for early diagnosis of cancer and for monitoring of tumor behavior and response to targeted therapy. Effects of micro-RNAs on mucin gene expression have also started to emerge. In this review, we discuss the current views on epigenetic mechanisms of regulation of mucin genes (MUC1, MUC2, MUC3A, MUC4, MUC5AC, MUC5B, MUC6, MUC16, and MUC17) and the possible clinical applications of this epigenetic information

    Long- and short-range correlations and their event-scale dependence in high-multiplicity pp collisions at 1as = 13 TeV

    Get PDF
    Two-particle angular correlations are measured in high-multiplicity proton-proton collisions at s = 13 TeV by the ALICE Collaboration. The yields of particle pairs at short-( 06\u3b7 3c 0) and long-range (1.6 < | 06\u3b7| < 1.8) in pseudorapidity are extracted on the near-side ( 06\u3c6 3c 0). They are reported as a function of transverse momentum (pT) in the range 1 < pT< 4 GeV/c. Furthermore, the event-scale dependence is studied for the first time by requiring the presence of high-pT leading particles or jets for varying pT thresholds. The results demonstrate that the long-range \u201cridge\u201d yield, possibly related to the collective behavior of the system, is present in events with high-pT processes as well. The magnitudes of the short- and long-range yields are found to grow with the event scale. The results are compared to EPOS LHC and PYTHIA 8 calculations, with and without string-shoving interactions. It is found that while both models describe the qualitative trends in the data, calculations from EPOS LHC show a better quantitative agreement for the pT dependency, while overestimating the event-scale dependency. [Figure not available: see fulltext.

    First measurement of the |t|-dependence of coherent J/ψ photonuclear production

    Get PDF

    Charged-particle multiplicity fluctuations in Pb–Pb collisions at √sNN = 2.76 TeV

    Get PDF
    Measurements of event-by-event fluctuations of charged-particle multiplicities in Pb–Pb collisions at √sNN = 2.76 TeV using the ALICE detector at the CERN Large Hadron Collider (LHC) are presented in the pseudorapidity range |η|<0.8 and transverse momentum 0.2<pT<2.0 GeV/c. The amplitude of the fluctuations is expressed in terms of the variance normalized by the mean of the multiplicity distribution. The η and pT dependences of the fluctuations and their evolution with respect to collision centrality are investigated. The multiplicity fluctuations tend to decrease from peripheral to central collisions. The results are compared to those obtained from HIJING and AMPT Monte Carlo event generators as well as to experimental data at lower collision energies. Additionally, the measured multiplicity fluctuations are discussed in the context of the isothermal compressibility of the high-density strongly-interacting system formed in central Pb–Pb collisions.publishedVersio

    Pion-kaon femtoscopy and the lifetime of the hadronic phase in Pb-Pb collisions at root(S)(NN)=2.76 TeV

    Get PDF
    In this paper, the first femtoscopic analysis of pion-kaon correlations at the LHC is reported. The analysis was performed on the Pb-Pb collision data at root(S)(NN) = 2.76 TeV recorded with the ALICE detector. The non-identical particle correlations probe the spatio-temporal separation between sources of different particle species as well as the average source size of the emitting system. The sizes of the pion and kaon sources increase with centrality, and pions are emitted closer to the centre of the system and/or later than kaons. This is naturally expected in a system with strong radial flow and is qualitatively reproduced by hydrodynamic models. ALICE data on pion-kaon emission asymmetry are consistent with (3+1)-dimensional viscous hydrodynamics coupled to a statistical hadronisation model, resonance propagation, and decay code THERMINATOR 2 calculation, with an additional time delay between 1 and 2 fm/c for kaons. The delay can be interpreted as evidence for a significant hadronic rescattering phase in heavy-ion collisions at the LHC. (C) 2020 The Author. Published by Elsevier B.V.Peer reviewe
    • 

    corecore