13 research outputs found

    Cancer Biomarker Discovery: The Entropic Hallmark

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    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

    Geriatrie

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    Responsiveness of isolated thoracic aorta to norepinephrine and acetylcholine in cold-acclimated rats

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    We investigated the responses of thoracic aortae to adrenergic contraction and endothelium-dependent relaxation following chronic exposure to cold in rats. Two groups (CA, cold-acclimated for 12 weeks at 5 °C; WA, warm-acclimated for 12 weeks at 24 °C) of 10 male Sprague-Dawley rats were used. After anesthesia, the thoracic aortae (4 mm long) were isolated and the vascular tension was measured with a force transducer. The dose-response relations for aortic responses to norepinephrine (NE), phenylephrine (PE) and acetylcholine (Ach) were determined and compared between the CA and the WA groups. In the CA rats, the thoracic aortae became more sensitive to Ach-induced vasorelaxation. The vascular sensitivities to NE- or PE-induced contraction in the thoracic aortae were lowered. Chronic exposure to cold decreased NE- and PE-induced vasoconstrictive responses and increased Achinduced vasorelaxative response of the isolated thoracic aortae, which were suggested to be due to enhanced release of NE-induced endothelium-derived relaxing factor by up-regulating endothelial α1-adrenoceptors

    Thermoregulation in mice exhibits genetic variability early in senescence

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    Aging leads to a loss of thermoregulation that can be readily monitored in laboratory mice. However, it is unclear from previous studies—we provide a tabular summary of 15 articles—whether significant loss occurs by midlife (∼15 months of age). In this study, we examined 34 females from 22 LSXSS strains starting at 4 and 8 months of age (17 mice per age group). We used transponders inserted just under the loose skin of the pelt and calibrated against rectal body temperature to measure temperatures quickly without restraint. We found that the mean body temperatures measured 5 months later (9 and 13 months of age) had dropped significantly below normal in both groups: 0.6ºC lower in the younger cohort and 1.0ºC lower in the older cohort. These drops were not associated with weight loss or signs of pathology. Notably, the loss of thermoregulation between 8 and 13 months of age also exhibited genetic variation that was highly significant (P = 0.004). Such variation is potentially a powerful tool for determining the cause of thermoregulatory loss with age and whether this loss predicts senescence changes later in life, including the force of mortality
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