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

In situ Effect of Nanohydroxyapatite Paste in Enamel Teeth Bleaching

Federal University of Para. Department of Restorative Dentistry. Belem, PA, Brazil.Federal University of Para. Department of Restorative Dentistry. Belem, PA, Brazil.Federal University of Para. Department of Restorative Dentistry. Belem, PA, Brazil.Federal University of Para. Department of Restorative Dentistry. Belem, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Departamento de Toxicologia. Ananindeua, PA, Brasil.Federal University of Para. Department of Restorative Dentistry. Belem, PA, Brazil.AIM: Evaluate in situ the effect of nanohydroxyapatite paste (nano-HAP) before bleaching with hydrogen peroxide 35% (HP35%) by ion chromatography (IC) Knoop hardness number (KHN) and tristimulus colorimetry (TC). MATERIALS AND METHODS: A total of 60 fragments were obtained from third molars included (3 mm × 3 mm × 3 mm) and the specimens were divided into three groups (n = 20): Gas chromatography (CG) (negative control group) = no bleaching; HP35% (positive control group) = HP35% whitening (whiteness HP35%); nano-HAP = application for 10 minutes before bleaching treatment + HP35%. The specimens were fixed to the volunteers' molars. The KHN and TC were measured before and after bleaching. For IC, the dentin layer was removed, leaving the enamel that was crushed, and autoclaved for chemical quantification (calcium, fluorine, and phosphorus). The results of KHN and TC were analyzed statistically by analysis of variance (ANOVA) followed by Tukey test (p < 0.05). RESULTS: The HP35% group showed reduction of the Ca, F, and P ions. The initial and final KHN mean of the CG and nano-HAP did not differ statistically; however, the group of HP35% did differ statistically. The mean ΔE of the HP35% and nano-HAP groups did not differ statistically from each other. However, they differed from the CG. CONCLUSION: The nano-HAP paste preserved the KHN, promoted the lower loss of Ca and P ions and an increase of F ions when compared with the CG, but did not influence the effectiveness of the bleaching treatment. CLINICAL SIGNIFICANCE: Nano-HA is a biomaterial that has shown positive results in the prevention of deleterious effects on the enamel by the action of the office bleaching treatment