Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis

<p>Abstract</p> <p>Background</p> <p>The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling.</p> <p>Methods</p> <p>The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, <it>GLUT3</it>, <it>HSAL2</it>, and <it>PACE4</it>, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR.</p> <p>Results</p> <p>Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, <it>MMP-1</it> encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of <it>GLUT3</it>, <it>HSAL2</it> and <it>PACE4</it>, respectively. Univariate analyses demonstrated that <it>GLUT3</it> over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). <it>HSAL2</it> was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only <it>GLUT3</it> showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). <it>PACE4</it> mRNA expression failed to show correlation with any of the relevant parameters. </p> <p>Conclusion</p> <p>The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.</p

Spatial distribution of bivalves in relation to environmental conditions (middle Danube catchment, Hungary)

The spatial distribution of bivalves in relation to environmental conditions was studied along a second- and third order stream – medium-sized river (River Ipoly) – large river (River Danube) continuum in the Hungarian Danube River system. Quantitative samples were collected four times in 2007 and a total of 1662 specimens, belonging to 22 bivalve species were identified. Among these species, two are endangered (Pseudanodonta complanata, Unio crassus) and five are invasive (Dreissena polymorpha, D. rostriformis bugensis, Corbicula fluminea, C. fluminalis, Anodonta woodiana) in Hungary. The higher density presented by Pisidium subtruncatum, P. supinum, P. henslowanum and C. fluminea suggests that these species may have a key role in this ecosystem. Three different faunal groups were distinguished but no significant temporal change was detected. The lowest density and diversity with two species (P. casertanum and P. personatum) occurred in streams. The highest density and diversity was found in the River Ipoly, in the side arms of the Danube and in the main arm of the Danube with sand and silt substrate, being dominated by P. subtruncatum and P. henslowanum. Moderate density and species richness were observed in the main arm of the Danube with pebble and stone substrate, being dominated by C. fluminea and S. rivicola. Ten environmental variables were found to have significant influence on the distribution of bivalves, the strongest explanatory factors being substrate types, current velocity and sedimentological characteristics.The project was financially supported by the Hungarian Scientific Research Fund under the contract No. OTKA T/046180. Special thanks to the DanubeIpoly National Park for the help in field work.info:eu-repo/semantics/publishedVersio

Identification of Novel Inhibitors of Dietary Lipid Absorption Using Zebrafish

Pharmacological inhibition of dietary lipid absorption induces favorable changes in serum lipoprotein levels in patients that are at risk for cardiovascular disease and is considered an adjuvant or alternative treatment with HMG-CoA reductase inhibitors (statins). Here we demonstrate the feasibility of identifying novel inhibitors of intestinal lipid absorption using the zebrafish system. A pilot screen of an unbiased chemical library identified novel compounds that inhibited processing of fluorescent lipid analogues in live zebrafish larvae. Secondary assays identified those compounds suitable for testing in mammals and provided insight into mechanism of action, which for several compounds could be distinguished from ezetimibe, a drug used to inhibit cholesterol absorption in humans that broadly inhibited lipid absorption in zebrafish larvae. These findings support the utility of zebrafish screening assays to identify novel compounds that target complex physiological processes

Experimental Detritus Manipulations Unite Surface and Cave Stream Ecosystems Along a Common Energy Gradient

Subsidies of detritus from donor habitats are important energy sources for many ecosystems, but understanding their role in structuring recipient food webs requires comparative experimental studies along the full spectrum of detrital fluxes. Here we report results from an experimental addition of maize (Zea mays L.) litter to a detritus-poor cave stream ecosystem, which we then compare with analogous, past experiments using detritus-rich surface stream ecosystems that similarly have detritus-based food webs and extremely low in situ primary production. Bulk-tissue and compound-specific stable isotope analyses showed that maize litter carbon (C) was rapidly assimilated by microbes and transferred via successive trophic levels to the top of the cave stream food web (omnivorous crayfishes and predatory salamanders). All trophic levels increased in abundance and biomass, but only facultative cave taxa, that is those also found in surface streams, contributed to this numerical response. The lack of response by obligate cave species presumably occurred because evolutionary trade-offs associated with adaptations to low-C environments constrained their population-level responses during the one-year period of the litter addition. Comparison of the responses of the cave community with the analogous litter manipulation experiments in surface streams showed strong convergence in the functional relationship between invertebrate and detritus biomass (R 2 = 0.72, P \u3c 0.0001). Our results suggest that these seemingly disparate stream food webs lie along a single, common gradient of detritus supply, occupied at its extreme minimum by communities of obligate cave taxa adapted to low-energy environments