OPCML Is a Broad Tumor Suppressor for Multiple Carcinomas and Lymphomas with Frequently Epigenetic Inactivation

Background: Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction. Methodology/Principal Findings: Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -indendent growth of carcinoma cells with endogenous silencing. Conlusions/Significance: Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies. © 2008 Cui et al.published_or_final_versio

Measurement imperatives and their impact: Academic staff narratives on riding the metric tide

Higher education is in the grip of an unprecedented level of attention to quantitative performance indicators. The recent trajectory of government policy discourses position such measures as necessary in enabling students to have more and better information to inform their choices, in ensuring that institutions are more transparent in their offer, and in justifying to the public that government funding for higher education is well-spent. Measurement imperatives are, therefore, positioned in policy discourses as key to the generation of market competition and institutional differentiation. But beyond government policymakers, many are sceptical about their use and value. Some consider that the measures themselves are flawed instruments; some are concerned about their role in increasing surveillance of staff; and some feel they have little value in relation to enhancing knowledge and knowing, improving pedagogic relationships and developing learning communities. This chapter uses a narrative approach to explore these tensions. It includes five academics’ accounts of their personal responses to measurement imperatives. In tracing how individual narratives intersect with broader discourses of marketisation, equity and differentiation, the chapter activates the sociological imagination (C. Wright Mills, 1959) to bring into closer view some vital questions about the aims, purpose and value of contemporary higher education

Of saints, sows or smiths? Copper-brazed iron handbells in Early Medieval England

Copper-brazed iron handbells were a distinctive feature of monastic life in Early Medieval Ireland, Scotland and Wales. Handbells were used in liturgy, prayer, worship, and later as reliquaries. In England, brazed bells of the 7th to 9th centuries take on a greater range of sizes and forms and are found on a wider variety of sites. As a consequence, their roles within Christianity have been questioned, and associations with animals and itinerant smiths have been emphasised instead. Recent archaeological investigation of an Anglo-Saxon marsh-island at Little Carlton, Lincolnshire has resulted in one of the largest assemblages of copper-brazed iron bells from any site in England, comparable to similar collections from Flixborough and Brandon. Taking into consideration the inclusion of brazen bells in some ritualistic ‘closure hoards’, this paper argues that whilst Anglo-Saxon plain iron bells may have fulfilled a range of profane functions, those that were copper-brazed, regardless of their size, were important objects amongst early Christian communities in England, and the Northumbrian church in particular

The IgLON Family in Epithelial Ovarian Cancer: Expression Profiles and Clinicopathologic Correlates

Purpose: The IgLON family of cell adhesion molecules, comprising OPCML, HNT, LSAMP, and NEGR1, has recently been linked to cancer, through two of its members being proposed as tumor suppressors. We examined the expression profile of the family in human sporadic epithelial ovarian cancer and the normal ovary. Experimental Design: We determined the expression level of each IgLON in a panel comprising 57 tumor and 11 normal ovarian samples by quantitative real-time reverse transcription-PCR. The results were statistically tested for associations with clinicopathologic variables. Results: OPCML, LSAMP and NEGR1 exhibited reduced expression in the tumor samples relative to the normal samples, whereas HNT expression was elevated. Statistically significant changes were specific to histologic type. The expression levels of individual IgLONs were correlated, the most significant finding being a positive correlation between LSAMP and NEGR1. LSAMP expression was also negatively correlated with overall survival and was found to be a negative predictor of outcome. Conclusions: The expression of the IgLON family is altered in sporadic epithelial ovarian tumors in comparison to the normal ovary. In our small but representative cohort of patients, we have found significant correlations and associations in expression and clinicopathology that suggest a wider role of the family in ovarian cancer.NO DIVISION11pub451pu