Dataset Information

The role of circulating cell-free DNA as an inflammatory mediator after stroke.

ABSTRACT: Stroke is the second leading cause of death worldwide and a leading cause of disability. Clinical and experimental studies highlighted the complex role of the immune system in the pathophysiology of stroke. Ischemic brain injury leads to the release of cell-free DNA, a damage-associated molecular pattern, which binds to pattern recognition receptors on immune cells such as toll-like receptors and cytosolic inflammasome sensors. The downstream signaling cascade then induces a rapid inflammatory response. In this review, we are highlighting the characteristics of cell-free DNA and how these can affect a local as well as a systemic response after stroke. For this purpose, we screened literature on clinical studies investigating cell-free DNA concentration and properties after brain ischemia. We report the current understanding for mechanisms of DNA uptake and sensing in the context of post-stroke inflammation. Moreover, we compare possible treatment options targeting cell-free DNA, DNA-sensing pathways, and the downstream mediators. Finally, we describe clinical implications of this inflammatory pathway for stroke patients, open questions, and potential future research directions.

SUBMITTER: Roth S

PROVIDER: S-EPMC10279574 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The role of circulating cell-free DNA as an inflammatory mediator after stroke.

Roth Stefan S Wernsdorf Saskia R SR Liesz Arthur A

Seminars in immunopathology 20230522 3

Stroke is the second leading cause of death worldwide and a leading cause of disability. Clinical and experimental studies highlighted the complex role of the immune system in the pathophysiology of stroke. Ischemic brain injury leads to the release of cell-free DNA, a damage-associated molecular pattern, which binds to pattern recognition receptors on immune cells such as toll-like receptors and cytosolic inflammasome sensors. The downstream signaling cascade then induces a rapid inflammatory r ...[more]

PMID: 37212886

Similar Datasets

Project description:BackgroundOncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated.Methods and findingsCirculating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test.ConclusionsPrognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.

Dataset Information

The role of circulating cell-free DNA as an inflammatory mediator after stroke.

Publications

The role of circulating cell-free DNA as an inflammatory mediator after stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets