Cellular Mechanisms of Oxidative Stress and Action in Melanoma

Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment

Heavy metals and epigenetic alterations in brain tumors

Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature

Potential Role of Carbon Nanomaterials in the Treatment of Malignant Brain Gliomas

Malignant gliomas are the most common primary brain tumors in adults up to an extent of 78% of all primary malignant brain tumors. However, total surgical resection is almost unachievable due to the considerable infiltrative ability of glial cells. The efficacy of current multimodal therapeutic strategies is, furthermore, limited by the lack of specific therapies against malignant cells, and, therefore, the prognosis of these in patients is still very unfavorable. The limitations of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent to brain tumors, are major reasons for this unsolved clinical problem. The major problem in brain drug delivery is the presence of the blood–brain barrier, which limits the delivery of many chemotherapeutic agents. Nanoparticles, thanks to their chemical configuration, are able to go through the blood–brain barrier carrying drugs or genes targeted against gliomas. Carbon nanomaterials show distinct properties including electronic properties, a penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, a large surface area, and easy modification with molecules, which render them as suitable candidates for deliver drugs. In this review, we will focus on the potential effectiveness of the use of carbon nanomaterials in the treatment of malignant gliomas and discuss the current progress of in vitro and in vivo researches of carbon nanomaterials-based drug delivery to brain

Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin-1β Production during Infection

<div><p>Previous studies have shown that the pro-inflammatory cytokine IL-1β has a crucial role in host defenses against group B streptococcus (GBS), a frequent human pathogen, by recruiting neutrophils to infection sites. We examined here the cell types and mechanisms involved in IL-1β production during infection. Using a GBS-induced peritonitis model in mice, we first found that a large proportion of exudate cells contain intracellular IL-1β by immunofluorescence. Of the IL-1β positive cells, 82 and 7% were neutrophils and macrophages, respectively, suggesting that the former cell type might significantly contribute to IL-1β production. Accordingly, depletion of neutrophils with anti-Ly6G antibodies resulted in a significant reduction in the levels of IL-1β, but not of TNF-α or IL-6. We next found that neutrophils are capable of releasing mature IL-1β and TNF-α directly in response to <i>in vitro</i> stimulation with GBS. The production of pro-IL-1β and TNF-α in these cells required the Toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B1, which is involved in mobilization of a subfamily of TLRs to the endosomes. Moreover, pro-IL-1β processing and IL-1β release was triggered by GBS hemolysin and required components of the canonical inflammasome, including caspase-1, ASC and NLRP3. Collectively our findings indicate that neutrophils make a significant contribution to IL-1β production during GBS infection, thereby amplifying their own recruitment. These cells directly recognize GBS by means of endosomal TLRs and cytosolic sensors, leading to activation of the caspase-1 inflammasome.</p></div