Dosage and characterization of circulating DNA: present usage and possible applications in systemic autoimmune disorders

Gargiulo, Mauro; Morozzi, Gabriella; Piccini, Monica; Chen, J; Bellisai, Francesca; Fineschi, Silvia; Marcolongo, Roberto

doi:10.1016/s1568-9972(02)00101-5

Cited by 62 publications

(40 citation statements)

References 29 publications

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“…The predominant procoagulant role of cell-free polyanionic RNA over DNA particularly in vivo is likely due to the immediate exposure of RNA in the extracellular space after cell damage, whereas the majority of DNA may still be contained in complexed form together with histones in the nuclei and thereby is far less accessible to coagulation factors (34). Moreover, only sufficiently large RNA molecules with a minimal size of Ϸ50 nucleotides were found to augment enzyme-substrate reactions involving a template-type mechanism, and semiquantative estimation of affinities for RNA-protein binding (derived from mobility shift assay) revealed values in the nM range (15).…”

Section: Discussionmentioning

confidence: 99%

Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation

Kannemeier

Shibamiya²,

Nakazawa

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

492

467

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Upon vascular injury, locally controlled haemostasis prevents lifethreatening blood loss and ensures wound healing. Intracellular material derived from damaged cells at these sites will become exposed to blood components and could contribute to blood coagulation and pathological thrombus formation. So far, the functional and mechanistic consequences of this concept are not understood. Here, we present in vivo and in vitro evidence that different forms of eukaryotic and prokaryotic RNA serve as promoters of blood coagulation. Extracellular RNA was found to augment (auto-)activation of proteases of the contact phase pathway of blood coagulation such as factors XII and XI, both exhibiting strong RNA binding. Moreover, administration of exogenous RNA provoked a significant procoagulant response in rabbits. In mice that underwent an arterial thrombosis model, extracellular RNA was found associated with fibrin-rich thrombi, and pretreatment with RNase (but not DNase) significantly delayed occlusive thrombus formation. Thus, extracellular RNA derived from damaged or necrotic cells particularly under pathological conditions or severe tissue damage represents the long sought natural ''foreign surface'' and provides a procoagulant cofactor template for the factors XII/XI-induced contact activation/amplification of blood coagulation. Extracellular RNA thereby reveals a yet unrecognized target for antithrombotic intervention, using RNase or related therapeutic strategies.contact phase activation ͉ thrombosis ͉ RNase ͉ vascular injury ͉ wound healing

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Section: Discussionmentioning

confidence: 99%

Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation

Kannemeier

Shibamiya²,

Nakazawa

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

492

467

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“…including cancer [7][8][9]. The cell-free DNA (cfDNA) enters the circulation by direct secretion from the tumor cells, by apoptosis, necrosis, from circulating tumor cells, and from the normal surrounding tissues [10][11][12][13].…”

Section: Metastatic Colorectal Cancermentioning

confidence: 99%

Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

Spindler

2016

Acta Oncologica

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Background: Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment. This review aims to present the current literature which has specifically reported data on the potential utility of cfDNA and on tumor-specific mutations in metastatic colorectal cancer (mCRC). Method: Methodological, biological and clinical aspects are discussed based on the most recent development in this specific setting, and eligible studies were identified by systematic literature searched from Pubmed and EMBASE in addition to conference papers and communications. Results: The literature regarding cfDNA in CRC is broad and heterogeneous concerning aims, nomenclature, methods, cohorts and clinical endpoints and consequently difficult to include in a single systematic search. However, the available data underline a strong clinical value of measuring both total cfDNA levels and tumor-specific mutations in the plasma of patients with mCRC, pre-and during systemic therapy. Conclusion: This paper had gathered the most recent literature on several aspects of cfDNA in mCRC, including methodological, biological and clinical aspects, and discussed the large clinical potential in this specific setting, which needs to be validated in carefully designed prospective studies in statistically relevant cohorts.

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“…Serum levels of nucleosomal DNA fragments are significantly increased in various autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. (56) Particularly intensive investigations of exNA were performed in order to develop blood-based tests for cancer (Table 1, Fig. 2).…”

Section: Exna In Diagnosticsmentioning

confidence: 99%

Extracellular nucleic acids

Vlassov¹,

Laktionov²,

Rykova³

2007

BioEssays

156

102

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Extracellular nucleic acids are found in different biological fluids in the organism and in the environment: DNA is a ubiquitous component of the organic matter pool in the soil and in all marine and freshwater habitats. Data from recent studies strongly suggest that extracellular DNA and RNA play important biological roles in microbial communities and in higher organisms. DNA is an important component of bacterial biofilms and is involved in horizontal gene transfer. In recent years, the circulating extracellular nucleic acids were shown to be associated with some diseases. Attempts are being made to develop noninvasive methods of early tumor diagnostics based on analysis of circulating DNA and RNA. Recent observations demonstrated the possibility of nucleic acids exchange between eukaryotic cells and extracellular space suggesting their participation in so far unidentified biological processes.

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Dosage and characterization of circulating DNA: present usage and possible applications in systemic autoimmune disorders

Cited by 62 publications

References 29 publications

Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation

Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation

Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

Extracellular nucleic acids

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