The Higgs as a Portal to Plasmon-like Unparticle Excitations

12 LaTeX pages, 2 figures.-- Published in: JHEP04(2008)028.-- Final full-text version available at: http://dx.doi.org/10.1088/1126-6708/2008/04/028.A renormalizable coupling between the Higgs and a scalar unparticle operator O_U of non-integer dimension d_U<2 triggers, after electroweak symmetry breaking, an infrared divergent vacuum expectation value for O_U. Such IR divergence should be tamed before any phenomenological implications of the Higgs-unparticle interplay can be drawn. In this paper we present a novel mechanism to cure that IR divergence through (scale-invariant) unparticle self-interactions, which has properties qualitatively different from the mechanism considered previously. Besides finding a mass gap in the unparticle continuum we also find an unparticle pole reminiscent of a plasmon resonance. Such unparticle features could be explored experimentally through their mixing with the Higgs boson.Work supported in part by the European Commission under the European Union through the Marie Curie Research and Training Networks “Quest for Unification” (MRTN-CT- 2004-503369) and “UniverseNet” (MRTN-CT-2006-035863); by the Spanish Consolider- Ingenio 2010 Programme CPAN (CSD2007-0042); by a Comunidad de Madrid project (P-ESP-00346) and by CICYT, Spain, under contracts FPA 2007-60252 and FPA 2005-02211

HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker. METHODS: 85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis. RESULTS: HIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1α expression specified a subgroup of high-risk patients (p < 0.05). CONCLUSION: HIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy

Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity

BACKGROUND: Intermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCC's) of the oral cavity. METHODS: 308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Ck's), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis. RESULTS: The expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCC's and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin. CONCLUSION: The expression of Ck 8/18 in SCC's of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCC's

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family

High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6-RUNX1-positive acute lymphoblastic leukemia

Item does not contain fulltextBACKGROUND: Assessment of minimal residual disease (MRD) is an integral component for response monitoring and treatment stratification in acute lymphoblastic leukemia (ALL). We aimed to evaluate the genomic ETV6-RUNX1 fusion sites as a single marker for MRD quantification. PROCEDURE: In a representative, uniformly treated cohort of pediatric relapsed ALL patients (n = 52), ETV6-RUNX1 fusion sites were compared to the current gold standard, immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements. RESULTS: Primer/probe sets designed to ETV6-RUNX1 fusions achieved significantly more frequent a sensitivity and a quantitative range of at least 10(-4) compared to the gold standard with 100% and 73% versus 76% and 47%, respectively. The breakpoint sequence was identical at diagnosis and relapse in all tested cases. There was a high degree of concordance between quantitative MRD results assessed using ETV6-RUNX1 and the highest Ig/TCR marker (Spearman's 0.899, P (1/2) log-step in only 6% of patients. A high proportion of ETV6-RUNX1-positive ALL relapses (40%) in our cohort showed a poor response to induction treatment at relapse, and therefore had an indication for hematopoietic stem cell transplantation, demonstrating the need of accurate identification of this subgroup. CONCLUSIONS: ETV6-RUNX1 fusion sites are highly sensitive and reliable MRD markers. Our data confirm that they are unaffected by clonal evolution and selection during front-line and second-line chemotherapy in contrast to Ig/TCR rearrangements, which require several markers per patient to compensate for the observed loss of target clones. In future studies, the genomic ETV6-RUNX1 fusion can be used as single MRD marker

Can immunohistochemistry serve as an alternative to subjective histopathological diagnosis of oral epithelial dysplasia?

Many attempts have been made to identify objective molecular biomarkers to diagnose and prognosticate oral epithelial dysplasia (OED) because histopathological interpretation is subjective and lacks sensitivity. The majority of these efforts describe changes in gene expression at protein level in OED as determined by immunohistochemistry (IHC). However, the literature on these putative markers of oral cancer progression is vast and varied.The main purpose of this article is to review current knowledge on biomarkers of protein expression for OED by IHC approaches. We further discuss these findings in terms of the proposed essential hallmarks of cancer cells to better understand their role in oral oncogenesis

The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy

<p>Abstract</p> <p>Purpose</p> <p>Androgens stimulate the production of hypoxia-inducible factor (HIF1α) and ultimately vascular endothelial growth factor (VEGF-A). Additionally, epithelial growth factor (EGF) mediates HIF1α production. Carbonic anhydrase IX (CAIX) expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT).</p> <p>Materials and methods</p> <p>Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2), with prostate cancer (mean PSA, 13.3 ± 3.7), were treated with radiation therapy (RT, median dose, 74 Gy). Fifty seven (55.3%) patients received ADT (median duration, 6 months; range, 0 – 24). Median follow-up was 97.6 months (range, 5.9 – 206.8).</p> <p>Results</p> <p>Higher EGFR expression was significantly (<it>p</it> = 0.04) correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (<it>p</it> = 0.02) prognostic factor for biological progression-free survival (bPFS). A trend towards significance (<it>p</it> = 0.05) was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (<it>p</it> = 0.01) and high EGFR (<it>p</it> = 0.04) expression remained significant adverse prognostic factors.</p> <p>Conclusions</p> <p>Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.</p