Gene expression analysis of cell death induction by Taurolidine in different malignant cell lines

<p>Abstract</p> <p>Background</p> <p>The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types.</p> <p>Methods</p> <p>Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3) were incubated with TRD (100 μM, 250 μM and 1000 μM). Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the <it>Agilent </it>-microarray platform to indentify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to <it>Ingenuity Pathways Analysis </it>and selected genes were validated by qRT-PCR and Western Blot.</p> <p>Results</p> <p>TRD 250 μM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3) as well as genes involved in the ER stress response (PPP1R15A), in ubiquitination (TRAF6) and mitochondrial apoptotic pathways (PMAIP1).</p> <p>Conclusions</p> <p>This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis.</p

Enhanced recovery in colorectal surgery: a multicentre study

<p>Abstract</p> <p>Background</p> <p>Major colorectal surgery usually requires a hospital stay of more than 12 days. Inadequate pain management, intestinal dysfunction and immobilisation are the main factors associated with delay in recovery. The present work assesses the short and medium term results achieved by an enhanced recovery program based on previously published protocols.</p> <p>Methods</p> <p>This prospective study, performed at 12 Spanish hospitals in 2008 and 2009, involved 300 patients. All patients underwent elective colorectal resection for cancer following an enhanced recovery program. The main elements of this program were: preoperative advice, no colon preparation, provision of carbohydrate-rich drinks one day prior and on the morning of surgery, goal directed fluid administration, body temperature control during surgery, avoiding drainages and nasogastric tubes, early mobilisation, and the taking of oral fluids in the early postoperative period. Perioperative morbidity and mortality data were collected and the length of hospital stay and protocol compliance recorded.</p> <p>Results</p> <p>The median age of the patients was 68 years. Fifty-two % of the patients were women. The distribution of patients by ASA class was: I 10%, II 50% and III 40%. Sixty-four % of interventions were laparoscopic; 15% required conversion to laparotomy. The majority of patients underwent sigmoidectomy or right hemicolectomy. The overall compliance to protocol was approximately 65%, but varied widely in its different components. The median length of postoperative hospital stay was 6 days. Some 3% of patients were readmitted to hospital after discharge; some 7% required repeat surgery during their initial hospitalisation or after readmission. The most common complications were surgical (24%), followed by septic (11%) or other medical complications (10%). Three patients (1%) died during follow-up. Some 31% of patients suffered symptoms that delayed their discharge, the most common being vomiting or nausea (12%), dyspnoea (7%) and fever (5%).</p> <p>Conclusion</p> <p>The following of this enhanced recovery program posed no risk to patients in terms of morbidity, mortality and shortened the length of their hospital stay. Overall compliance to protocol was 65%. The following of this program was of benefit to patients and reduces costs by shortening the length of hospital stay. The implantation of such programmes is therefore highly recommended.</p

Innovative Business Approaches for the Reduction of Extreme Poverty and Marginality?

Extreme poverty is an immense political and market failure, wasting the potential of hundreds of millions of people. Investing in the creation of markets that include the extreme poor and marginalized should thus not only be considered as a charitable activity, but promises high returns on investments - in financial and humanitarian terms. However, while the potential of innovative business approaches to target the poor that live close to the poverty line is increasingly being recognised, the question remains how far these approaches can push the margin to also include those that are extremely poor. And how can those that are marginalized from development opportunities be brought into and benefit from market-based systems to improve the quality of their lives? The impressive rise of business approaches to combating poverty stems from a long history of debates on the role of businesses in society. From an initial focus on social objectives as an external add-on, leading business thinkers have increasingly been stressing the benefits for companies of integrating social considerations into their core business strategies, for instance by targeting lowincome consumers (or 'bottom of the pyramid' markets) or strengthening supply and distribution chains through the involvement of local communities as part of inclusive business strategies. Others - most notably Muhammed Yunus along with other social entrepreneurs - are taking this argument one step further, advocating the use of business strategies primarily to address social goals rather than for financial gains. Thus, in discussions on the role of business in society, profit maximisation as the primary objective of business operations is increasingly making way for business initiatives that are guided by social objectives. This trend is also being supported by growing interest among investors in financing enterprises that promote social or environmental objectives, either as their primary aim or in parallel with seeking to generate financial returns. How suitable these different approaches are to engage the poorest and marginalized depends in part on the extent to which they are able to involve the extreme poor themselves, their flexibility to direct business objectives towards the reduction of extreme poverty and marginality, and their ability to successfully operate with non-business public and civil society partners and in sectors of particular interest to the extreme poor. Further research and action is needed to identify outcome-focused indicators and measurement tools for social value creation, examine possible government measures to support business activities for the poorest, and consider complementarities between the different business approaches. While we recognise that it is unrealistic to expect businesses to be able to reach all of the extreme poor, we believe that the boundaries of innovative business operations can be pushed much further to include a far larger number of the poorest and marginalized

A chromosome conformation capture ordered sequence of the barley genome

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Angina pectoris in a 47-year-old athletic man with psoriasis vulgaris

A 47-year-old man presented with angina pectoris complaints in the chest pain unit. Due to psoriasis and psoriatic arthritis he had been systemically treated for 4 years. Because of an increased cardiovascular risk profile, coronary heart disease ( CHD) was suspected and an invasive coronary diagnosis was performed. In the cardiac catheterization, CHD could be detected and treated in the same session. The risk of CHD in patients with psoriasis is increased due to a higher incidence of risk factors but also the disease itself. Patients with psoriasis should regularly undergo cardiovascular risk screening