Covingtonlane6905
Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage.
Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermorresponse to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.
Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized patients with ABC to palbociclib alone or palbociclib plus the endocrine therapy received in the prior line of treatment. Moreover, we evaluated RB1 gene expression on CTCs and explored its prognostic role within the cTREnd subpopulation.
Forty-six patients with ER-positive, HER2-negative ABC were analyzed. Blood samples were collected before starting palbociclib treatment (timepoint T0), after the first cycle of treatment (timepoint T1), and at disease progression (timepoint T2). CTCs were isolated and counted by CellSearch® System using the CellSearch™Epithelial Cell kit. Progression-free survival (PFS), clinical benefit (CB) during study treatment, and time to treatment faring palbociclib response. Moreover, CTC count at the time of progression could predict clinical outcome post-palbociclib. RB1 expression analysis on CTCs is feasible and may provide additional prognostic information. Results should be interpreted with caution given the small studied sample size.
CTC count seems to be a promising modality in monitoring palbociclib response. Moreover, CTC count at the time of progression could predict clinical outcome post-palbociclib. RB1 expression analysis on CTCs is feasible and may provide additional prognostic information. Results should be interpreted with caution given the small studied sample size.
Environmental factors, such as oxidative stress, have the potential to modify the epigenetic landscape of cells. We have previously shown that DNA methyltransferase (DNMT) activity can be inhibited by sublethal doses of hydrogen peroxide (H
O
). However, site-specific changes in DNA methylation and the reversibility of any changes have not been explored. Using bead chip array technology, differential methylation was assessed in Jurkat T-lymphoma cells following exposure to H
O
.
Sublethal H
O
exposure was associated with an initial genome-wide decrease in DNA methylation in replicating cells, which was largely corrected 72h later. However, some alterations were conserved through subsequent cycles of cell division. Significant changes to the variability of DNA methylation were also observed both globally and at the site-specific level.
This research indicates that increased exposure to H
O
can result in long-term alterations to DNA methylation patterns, providing a mechanism for environmental factors to have prolonged impact on gene expression.
This research indicates that increased exposure to H2O2 can result in long-term alterations to DNA methylation patterns, providing a mechanism for environmental factors to have prolonged impact on gene expression.Along with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research response. The slow and inefficient process of carrying out traditional randomized clinical trials led regulatory authorities to hastily approve treatments and tests without sufficient evidence of safety and efficacy.We here outline issues with the current research platform, summarize shortcomings of traditional randomized clinical trials particularly apparent at the time of pandemics, and highlight the advantages of pragmatic clinical trials as an alternative to rapidly generate the needed clinical evidence. see more We further discuss barriers and challenges to pragmatic clinical trials implementation and explore opportunities for research institutions and regulatory authorities to facilitate widespread adoption of this vital research tool.As a subsequent wave of COVID-19, and/or another epidemic, are all but inevitable in our lifetime, we must ensure that our research infrastructure is conducive to carrying out pragmatic clinical trials to expeditiously generate the needed evidence and blunt the epidemic's toll on human lives and livelihoods.Malaria is a principal cause of illness and death in countries where the disease is endemic. Personal protection against mosquitoes using repellents could be a useful method that can reduce and/or prevent transmission of mosquito-borne diseases. The available repellent products, such as creams, roll-ons, and sprays for personal protection against mosquitoes, lack adequate long-term efficacy. In most cases, they need to be re-applied or replaced frequently. The encapsulation and release of the repellents from several matrices has risen as an alternative process for the development of invention of repellent based systems. The present work reviews various studies about the development and use of repellent controlled-release formulations such as polymer microcapsules, polymer microporous formulations, polymer micelles, nanoemulsions, solid-lipid nanoparticles, liposomes and cyclodextrins as new tools for mosquito-borne malaria control in the outdoor environment. Furthermore, investigation on the mathematical modelling used for the release rate of repellents is discussed in depth by exploring the Higuchi, Korsmeyer-Peppas, Weibull models, as well as the recently developed Mapossa model.
