Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Effect of Endodontic Chelating Solutions on The Bond Strength of Endodontic Sealers

The purpose of this in vitro study was to evaluate the effect of various chelating solutions on the radicular push-out bond strength of calcium silicate-based and resin-based root canal sealers. Root canals of freshly-extracted single-rooted teeth (n = 80) were instrumented by using rotary instruments. The specimens were randomly divided into 4 groups according to the chelating solutions being tested: (1) 17% ethylenediaminetetraacetic acid (EDTA); (2) 9% etidronic acid; (3) 1% peracetic acid (PAA); and (4) distilled water (control). In each group, the roots were further assigned into 2 subgroups according to the sealer used: (1) an epoxy resin-based sealer (AH Plus) and (2) a calcium silicate-based sealer (iRoot SP). Four 1 mm-thick sections were obtained from the coronal aspect of each root (n = 40 slices/group). Push-out bond strength test was performed at a crosshead speed of 1 mm/min., and the bond strength data were analyzed statistically with two-way analysis of variance (ANOVA) with Bonferroni's post hoc test (p 0.05). iRoot SP showed higher resistance to dislocation than AH Plus. Final irrigation with 17% EDTA, 9% Etidronic acid, and 1% PAA did not improve the bond strength of AH Plus and iRoot SP to radicular dentin.Wo