Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their value for detection of adenomas and adenocarcinomas

Expression of Transcribed Ultraconserved Regions (T-UCRs) is often deregulated in cancer. The present study assesses the expression and methylation of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal cancer (CRC) and explores the potential of T-UCR methylation in circulating DNA for the detection of adenomas and adenocarcinomas. Expression levels of Uc160, Uc283 and Uc346 were lower in neoplastic tissues from 64 CRC patients (statistically significant for Uc160, p<0.001), compared to non-malignant tissues, while methylation levels displayed the inverse pattern (p<0.001, p=0.001 and p=0.004 respectively). In colon cancer cell lines, overexpression of Uc160 and Uc346 led to increased proliferation and migration rates. Methylation levels of Uc160 in plasma of 50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis predicted the presence of CRC with 35% sensitivity and 89% specificity (p=0.016), while methylation levels of the combination of all three T-UCRs resulted in 45% sensitivity and 74.3% specificity (p=0.013). In conclusion, studied T-UCRs’ expression and methylation status are deregulated in CRC while Uc160 and Uc346 appear to have a complicated role in CRC progression. Moreover their methylation status appears a promising non-invasive screening test for CRC, provided that the sensitivity of the assay is improved

Business as Unusual: Designing products with consumers in the loop

This feasibility study was one of five feasibility studies on re-distributed manufacture, consumer goods and big data. The study looked mainly into: How could we engage users in NPD in future re-distributed models of sustainable production and consumption? To answer this question, the study mapped the different product-people interactions to identify the challenges and opportunities for user engagement in design and manufacture, to further investigate their application in order to bridge the gap between users, companies and the products that they produce. To further analyse these opportunities, two different product-people interactions were delved into, to understand how new forms of engaging people across the life cycle can achieve a more localised and responsive structures of manufacturing and product adoption. The results of these investigations helped to envision four contrasting scenarios of BaU, and generate conceptual business models and touchpoints to support these novel systems of consumption and production

Ulcerative colitis six years after colon cancer: only a coincidence?

Minas Sakellakis,1 Thomas Makatsoris,1 Maria Gkermpesi,2 Stavros Peroukidis,1 Haralabos Kalofonos11Division of Oncology, Department of Medicine, 2Department of Pathology, University, Hospital of Patras, Patras, GreeceAbstract: The association between inflammatory bowel disease and colorectal cancer is well known. Ulcerative colitis is a risk factor for the development of colorectal cancer, and this risk increases with the activity and duration of bowel inflammation. Here we describe the case of a 52-year-old man who developed ulcerative colitis 6 years after the diagnosis and treatment of colon cancer. Although this could be a coincidence, there could be additional possibilities, like pre-existence of quiescent colitis, late effect of therapy, or maybe the existence of common pathogenetic factors contributing to the development of ulcerative colitis and colorectal cancer.Keywords: ulcerative, colitis, colorectal, cancer, inflammatio

NF-kB2 genetic variations are significantly associated with non-small cell lung cancer risk and overall survival

During the last decade, a growing number of publications implicate NF-kB2 in NSCLC pathogenesis. Here, we investigated the clinical relevance of NF-kB2 single nucleotide polymorphisms (SNPs) rs7897947, rs11574852 and rs12769316 in NSCLC and their association with NF-kB2 protein and mRNA levels. Our data show that TT (rs7897947T >G) and AA (rs12769316G >A) genotypes were strongly associated with an increased risk for NSCLC (P = 0.019 and P = 0.003, respectively). Additionally, in multivariate analysis, TT (rs7897947T >G) homozygosity was associated with worse 2- and 3-year survival rates (P = 0.030 and P = 0.028, respectively), especially among patients with stages III/IV, who had worse 2, 3 and 5-year survival (P = 0.001, P = 0.022 and P = 0.035, respectively). In chemotherapy-treated patients, TT (rs12769316G >A) homozygosity was also associated with worse 2- and 3-year survival compared to G allele carriers (P = 0.006 and P = 0.014, respectively). Furthermore, rs12769316 was correlated with survival outcome of stage I and II patients (P = 0.031 and P = 0.006, respectively). Interestingly, amongst the patients who developed metastases, A allele carriers had better 5-year survival (P = 0.020). In addition, rs12769316 was associated with NF-kB2 protein (P = 0.001) and mRNA expression (P = 0.017) as well as with tumor maximum diameter (P = 0.025). Overall, this study suggests that rs7897947 and rs12769316 are involved in NSCLC susceptibility, in treatment response and in clinical outcome

Weekly docetaxel with or without gemcitabine as second-line chemotherapy in paclitaxel-pretreated patients with metastatic breast cancer: A randomized phase II study conducted by the hellenic co-operative oncology group

Objective: A randomized phase II trial was conducted to test whether the addition of gemcitabine to weekly docetaxel could improve the objective response rate and survival outcomes as second-line chemotherapy in patients with metastatic breast cancer who have failed a paclitaxel-containing regimen. Methods: Patients were randomized to receive either weekly docetaxel 40 mg/m2 (group A, n = 34) or the combination of weekly docetaxel 35 mg/m2 with gemcitabine 600 mg/m2 (group B, n = 41). Three consecutive weekly infusions followed by a 1-week rest period represented 1 chemotherapy cycle. Results: The objective response rate was 18% and 27.5% in group A and B, respectively (p = 0.413). No statistically significant differences were demonstrated in terms of median overall survival and time to disease progression. The rate and grade 3 and 4 neutropenia were higher in group B (23 vs. 3%). Conclusions: The weekly administration of docetaxel and gemcitabine did not result in superior clinical outcomes over weekly docetaxel. © 2009 S. Karger AG, Basel

The Matter Compiler-towards atomically precise engineering and manufacture

The Matter Compiler is a novel framework for a computer toolset that allows the design of arbitrary molecular structures and their assembly by means of radical synthesis pathways that resemble "pick and place". Such synthesis pathways have been demonstrated experimentally in the literature in the recent past using scanning probe microscopes (SPM). The Matter Compiler framework entails first-principles modelling and novel control approaches that together assess the feasibility of userdefined molecular structures, screen alternative options for their assembly and finally suggest synthesis by means of physical equipment such as scanning probe microscopes. Nanoscale structure design is driven by first-principles calculations as well as by any relevant physical and chemical knowledge that can be accessed by the system from chemical databases. The first main consideration is therefore a suitable modelling methodology enabling the design and assessment of user-defined molecular structures. This entails the computer representation of such structures, methods to access and use available chemical and physical knowledge and, subsequently, an overall approach to plan the synthesis of such structures. Currently, it is assumed that assembly takes place on suitable substrates molecule-by-molecule and uses firstprinciples calculations to determine synthesis pathways (plans) on those substrates. The second main consideration is to use those synthesis plans to determine how synthesis will take place within a physical instrument. For scanning probes, for example, this translates to a collection of set points for the instrument controller to follow that collectively comprise the trajectory of the scanning probe for each step of the process. Image processing for monitoring progress, visualization and haptic interaction are also part of the Matter Compiler-they provide insight, feedback and determination of intervention strategies in case of errors. In this paper a description of the Matter Compiler methodology and framework architecture is presented. Some computational results are also presented. © 2011 Collegium Basilea