Relevance of circulating nucleosomes and oncological biomarkers for predicting response to transarterial chemoembolization therapy in liver cancer patients

<p>Abstract</p> <p>Background</p> <p>Transarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers predicting therapy response are urgently required.</p> <p>Methods</p> <p>Here, sera of 50 prospectively and consecutively included HCC patients undergoing 71 TACE therapies were taken before and 3 h, 6 h and 24 h after TACE application to analyze concentrations of circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), alpha fetoprotein (AFP), C-reactive protein (CRP) and several liver biomarkers, and to compare these with radiological response to therapy.</p> <p>Results</p> <p>While nucleosomes, CYFRA 21-1, CRP and some liver biomarkers increased already 24 h after TACE, percental changes of nucleosome concentrations before and 24 h after TACE and pre- and posttherapeutic values of AFP, gamma-glutamyl-transferase (GGT) and alkaline phosphatase (AP) significantly indicated the later therapy response (39 progression versus 32 no progression). In multivariate analysis, nucleosomes (24 h), AP (24 h) and TACE number were independent predictive markers. The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC) curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity.</p> <p>Conclusion</p> <p>Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.</p

Veterinary students' usage and perception of video teaching resources

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to use a student-centred approach to develop an online video learning resource (called 'Moo Tube') at the School of Veterinary Medicine and Science, University of Nottingham, UK and also to provide guidance for other academics in the School wishing to develop a similar resource in the future.</p> <p>Methods</p> <p>A focus group in the format of the nominal group technique was used to garner the opinions of 12 undergraduate students (3 from year-1, 4 from year-2 and 5 from year-3). Students generated lists of items in response to key questions, these responses were thematically analysed to generate key themes which were compared between the different year groups. The number of visits to 'Moo Tube' before and after an objective structured practical examination (OSPE) was also analysed to provide data on video usage.</p> <p>Results</p> <p>Students highlighted a number of strengths of video resources which can be grouped into four overarching themes: (1) teaching enhancement, (2) accessibility, (3) technical quality and (4) video content. Of these themes, students rated teaching enhancement and accessibility most highly. Video usage was seen to significantly increase (P < 0.05) prior to an examination and significantly decrease (P < 0.05) following the examination.</p> <p>Conclusions</p> <p>The students had a positive perception of video usage in higher education. Video usage increases prior to practical examinations. Image quality was a greater concern with year-3 students than with either year-1 or 2 students but all groups highlighted the following as important issues: i) good sound quality, ii) accessibility, including location of videos within electronic libraries, and iii) video content. Based on the findings from this study, guidelines are suggested for those developing undergraduate veterinary videos. We believe that many aspects of our list will have resonance in other areas of medicine education and higher education.</p

A Comprehensive Analysis of the Dynamic Biological Networks in HCV Induced Hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, which is closely related to hepatitis C and cirrhosis. The molecular mechanisms underlying the hepatocarcinogenesis induced by HCV infection remain clarified from a standpoint of systems biology. By integrating data from protein-protein interactions, transcriptional regulation, and disease related microarray analysis, we carried out a dynamic biological network analysis on the progression of HCV induced hepatocarcinogenesis, and systematically explored the potentially disease-related mechanisms through a network view. The dysfunctional interactions among proteins and deregulatory relationships between transcription factors and their target genes could be causes for the occurrence and progression of this disease. The six pathologically defined disease stages in the development and progression of HCC after HCV infection were included in this study. We constructed disease-related biological networks for each disease stage, and identified progression-related sub-networks that potentially play roles in the developmental stage of the corresponding disease and participate in the later stage of cancer progression. In addition, we identified novel risk factors related to HCC based on the analysis of the progression-related sub-networks. The dynamic characteristics of the network reflect important features of the disease development and progression, which provide important information for us to further explore underlying mechanisms of the disease

A Meta-Analysis of Interleukin-8 -251 Promoter Polymorphism Associated with Gastric Cancer Risk

Background: Potential functional allele A/T single nucleotide polymorphism (SNP) of Interleukin 8 (IL-8) promoter-251has been implicated in gastric cancer risk. Methods: We aimed to explore the role of A/T SNP of IL-8-251 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Eighteen studies were ultimately eligible for the meta-analysis of IL-8- 251 A/T SNP. We adopted the most probably appropriate genetic model (codominant model). Potential sources of heterogeneity were sought out via stratification and sensitivity analyses, and publication biases were estimated. Results: Between IL-8-251 AA genotype with gastric cancer risk, statistically significant association could be noted with overall gastric cancer, evidently noted in Asians, witnessed in high quality subgroup, and apparently noted in intestinal-type gastric cancer. Conclusions: Our meta-analysis indicates that IL-8-251 AA genotype is associated with the overall risk of developing gastric cancer and may seem to be more susceptible to overall gastric cancer in Asian populations. IL-8-251 AA genotype is more associated with the intestinal-type gastric cancer. IL-8-251 AA genotype is not associated with Helicobacter Pylori infection status in our meta-analysis

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs

Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations ⩽5 μM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely. This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398. These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids

Towards the Human Colorectal Cancer Microbiome

Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions

Joint Practice Guidelines for Radionuclide Lymphoscintigraphy for Sentinel Node Localization in Oral/Oropharyngeal Squamous Cell Carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee