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Eyeing epigenetics
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[QUOTE="Milamber, post: 16145999, member: 340002"] Some of the most promising translational research involving epigenetic markers is being done in the area of cancer diagnosis and prognosis. In May 2018, Delphine Lissa, Pharm. D. and Ph.D., and her colleagues published the results of a retrospective study in [I]Lung Cancer[/I]. The study validated an assay that quantified methylation of a gene that codes for a DNA-binding transcription factor, called Homeobox A9 (HOXA9), which previous studies had identified as being associated with lung cancer. The current study goes a step further. “We showed that the methylation of HOXA9 is associated with higher risk in patients with early stage lung cancer,” said Lissa, a post-doctoral fellow at the National Cancer Institute. Researchers used digital droplet PCR (ddPCR) to quantify methylation of the HOXA9 gene in tumor samples. The technology uses oil droplets to divide the PCR solution into 20,000 smaller reactions, enabling more precise, digital quantification than standard PCR and making the technique highly sensitive. The resulting measurements of methylation in the current study, both alone and in combination with blood vessel invasion assessment (a negative predictor of survival), allowed researchers to stratify stage I patients with lung adenocarcinoma. “High methylation was associated with poor prognosis,” the authors wrote. These findings are important, Lissa said, because, currently, patients with lung adenocarcinoma at the same stage, experience different outcomes after surgery, the only curative option for these patients. Unfortunately, about one-third of the patients develop recurrence and die within five years, Lissa said. This methylation biomarker could help optimize therapy decisions for patients at high-risk for recurrence” Lissa said. Eventually, the goal is to find more such epigenetic or other biomarkers that could be included in a prognostic or diagnostic panel for patients with lung adenocarcinoma, Lissa said. For now, she and her collaborators will be working to validate the current assay and biomarker in a larger cohort of patients. They plan to do this in a prospective cohort, reproducing the current results. Future plans include using the assay on urine and in conjunction with liquid biopsy, retrieving tumor cells instead of using tumor tissue collected via standard biopsy. [B][B]Cardiovascular disease markers[/B][/B] Cardiovascular disease research is also currently focused on prognosis and identifying epigenetic markers that could be used in calculating risk of heart attacks in patients. That’s because, right now, only 60% to 80% of risk can be ascribed to genetics or lifestyle. “When you are talking about something that might kill you, you want much better certainty than that. On the risk-prediction side, we are using epigenetics,” said Svati Shah, M.D., associate professor of medicine and co-director of translational research within the Duke University’s Molecular Physiology Institute. In a November 2015 paper published in [I]PLOS Genetics[/I], a group led by Shah found endoplasmic reticulum (ER) stress to be associated with risk of future heart events. The group used genetics, transcriptomics, epigenetics, and metabolomics to identify two ER stress genes (BRSK2 and HOOK2) that were differentially methylated in blood taken from more than 3,500 patients referred for cardiac catheterization as part of the CATHGEN study. “ER stress has long been linked to Type 1 diabetes and Parkinson’s disease, among others, but this is the first indication that it is also playing a role in common heart attacks and death from heart disease,” Shah said at the time in a press release. [/QUOTE]
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