ABSTRACT
Glioblastoma (GB) is the most aggressive and common primary malignant tumor of the brain and central nervous system. Without treatment, the average patient survival time is about six months, which can be extended to fifteen months with multimodal therapies. The chemoresistance observed in GB is, in part, attributed to the presence of a subpopulation of glioblastoma-like stem cells (GSCs) that are characterized by heightened tumorigenic capacity and chemoresistance. GSCs are situated in hypoxic tumor niches, where they sustain and promote the stem-like phenotype and have also been correlated with high chemoresistance. GSCs have the particularity of generating high levels of extracellular adenosine (ADO), which causes the activation of the A3 adenosine receptor (A3AR) with a consequent increase in the expression and activity of genes related to chemoresistance. Therefore, targeting its components is a promising alternative for treating GB. This analysis determined genes that were up- and downregulated due to A3AR blockades under both normoxic and hypoxic conditions. In addition, possible candidates associated with chemoresistance that were positively regulated by hypoxia and negatively regulated by A3AR blockades in the same condition were analyzed. We detected three potential candidate genes that were regulated by the A3AR antagonist MRS1220 under hypoxic conditions: LIMD1, TRIB2, and TGFB1. Finally, the selected markers were correlated with hypoxia-inducible genes and with the expression of adenosine-producing ectonucleotidases. In conclusion, we detected that hypoxic conditions generate extensive differential gene expression in GSCs, increasing the expression of genes associated with chemoresistance. Furthermore, we observed that MRS1220 could regulate the expression of LIMD1, TRIB2, and TGFB1, which are involved in chemoresistance and correlate with a poor prognosis, hypoxia, and purinergic signaling.
ABSTRACT
Ionizing radiation of astrophysical origin might have played an important role in biological evolution during the long course of Earth's evolution. Several phenomena might have induced intense fluctuations in background ionizing radiation, such as highly energetic stellar explosions. There might also be anthropogenic causes for environmental radiation fluctuations, resulting from nuclear industry activities. The inclusion of these effects in a mathematical model for photosynthesis provides a useful tool to account for the damages of the above-mentioned phenomena in vegetal life. Mathematical models for photosynthesis typically only consider ultraviolet radiation and photosynthetically active radiation, as they have been a ubiquitous physical factor in the settlement of vegetal life. In this work a mathematical model for aquatic photosynthesis is modified, from first principles, to include the action of particulate ionizing radiation on the photosynthetic process. After assuming an ansatz allowing to separate damage/repair kinetics of ultraviolet and ionizing radiations, a treatable mathematical expression of the model is obtained. This generalized model is presented as a function of radiometric and photometric magnitudes, making it prone to calibration and useful to apply to aquatic ecosystems under radiational stress due to gamma-ray bursts, cosmic ray bursts, solar storms, or other sources of ionizing radiations.
Subject(s)
Models, Theoretical , Photosynthesis/radiation effects , Radiation, Ionizing , Phytoplankton/physiology , Phytoplankton/radiation effectsABSTRACT
Oscillating biochemical reactions are common in cell dynamics and could be closely related to the emergence of the life phenomenon itself. In this work, we study the dynamical features of some classical chemical or biochemical oscillators where the effect of cell volume changes is explicitly considered. Such analysis enables us to find some general conditions about the cell membrane to preserve such oscillatory patterns, of possible relevance to hypothetical primitive cells in which these structures first appeared.