1,721,027 research outputs found
Molecular damage and lung tumors in cigarette smoke-exposed mice
No full textCigarette smoke (CS) induces lung cancer through a multistep process that is now being depicted by molecular analyses. During the early phase (weeks), DNA damage occurs in nuclear and mitochondrial DNA, triggering adaptive responses activated by transient microRNA downregulation in the expression of defensive genes and proteins. During the intermediate phase (months), damaged cells are removed by apoptosis and the resulting cell loss is counteracted by a recruitment of stem cells that are highly sensitive to genotoxic damage. In parallel, microRNA downregulation becomes irreversible because of an accumulation of molecular damage in DICER. During the late phase (years), apoptosis efficacy is decreased by fragile histidine triad loss, while irreversible microRNA downregulation triggers the expression of mutated oncogenes, resulting in adenoma appearance. Furthermore, deletions occur in microRNA-encoding genes, causing carcinoma formation and uncontrolled growth. All reported pathogenic steps are required to obtain a fully developed lung cancer. This complex pathogenesis develops over a long period of time; therefore, it is difficult to induce cancer in short-living animals exposed to CS, whereas in humans there is a long latency from the start of smoke exposure to the onset of cancer
Special Issue: “Role of MicroRNA in Cancer Development and Treatment”
No full textExposure to environmental contaminants may lead to changes in the expression of microRNAs (miRNAs), resulting in several health effects [...
Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers
No full textInteraction between Helicobacter pylori, diet, and genetic polymorphisms as related to non-cancer diseases
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MiRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance
No full textGlutathione (GSH) is the most abundant antioxidant that contributes to regulating the cellular production of Reactive Oxygen Species (ROS) which, maintained at physiological levels, can exert a function of second messengers in living organisms. In fact, it has been demonstrated that moderate amounts of ROS can activate the signaling pathways involved in cell growth and proliferation, while high levels of ROS induce DNA damage leading to cancer development. Therefore, GSH is a crucial player in the maintenance of redox homeostasis and its metabolism has a role in tumor initiation, progression and therapy resistance. Our recent studies have demonstrated that neuroblastoma cells resistant to etoposide, a common chemotherapeutic drug, show a partial monoallelic deletion of the locus coding for miRNA 15a and 16-1. leading to a loss of these miRNAs and the activation of GSH-dependent responses. Therefore, the aim of this review is to highlight the role of specific miRNAs in the modulation of intracellular GSH levels in order to take into consideration the use of modulators of miRNA expression as a useful strategy to better sensitize tumors to current therapies
The Dysfunction of the Trabecular Meshwork During Glaucoma Course
No full textPrimary open angle glaucoma is a multi-tissue disease that targets, in an ascending order, the trabecular meshwork, the optic nerve head, the lateral geniculate nuclei, and the visual cortex. Oxidative stress and vascular damage play major roles in triggering apoptotic cell loss in these tissues. Molecular alterations occurring in the ocular anterior chamber during the early course of glaucoma trigger this cell loss. These molecular events are mainly of endogenous origin and related to the long-term accumulation of oxidative damages arising from mitochondrial failure and endothelial dysfunction. This situation results in decreased antioxidant defences in aqueous humour and apoptosis activation in trabecular meshwork cells as triggered by severe mitochondrial damage altering tissue function and integrity. The presence of neural proteins in glaucomatous aqueous humour indicate that a molecular interconnection exists between the anterior and the posterior chamber tissues. Trabecular meshwork and lamina cribrosa share a common neuro-ectodermal embryological, which contribute to explain the interconnection between anterior and the posterior chamber during glaucoma pathogenesis. During glaucoma, proteins deriving from the damage occurring in endothelial trabecular meshwork cells are released into aqueous humour. Accordingly, aqueous humour composition is characterised in glaucomatous patients by the presence of proteins deriving from apoptosis activation, mitochondrial damage, loss of intercellular connections, antioxidant decrease. Many questions remain unanswered, but molecular events illuminate TM damage and indicate that trabecular cell protection plays a role in the treatment and prevention of glaucoma
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