Interplay between LncRNAs and microRNAs in Breast Cancer.

(1) Although long noncoding RNAs (lncRNAs) are known to be precursors of microRNAs (miRNAs), they frequently act as competing endogoneous RNAs (ceRNAs), yet still their interplay with miRNA is not well known. However, their interaction with miRNAs may result in the modulation of miRNA action. (2) To determine the contribution of these RNA molecules in tumor resistance to chemotherapeutic drugs, it is essential to consider not only the oncogenic and tumor suppressive function of miRNAs but also the impact of lncRNAs on miRNAs. Therefore, we performed an extensive search in different databases including PubMed. (3) The present study concerns the interplay between lncRNAs and miRNAs in the regulatory post-transcriptional network and their impact on drugs used in the treatment of breast cancer. (4) Consideration of this interplay may improve the search for new drugs to circumvent chemoresistance.

Towards systematic nomenclature for cell-free DNA.

Cell-free DNA (cfDNA) has become widely recognized as a promising candidate biomarker for minimally invasive characterization of various genomic disorders and other clinical scenarios. However, among the obstacles that currently challenge the general progression of the research field, there remains an unmet need for unambiguous universal cfDNA nomenclature. To address this shortcoming, we classify in this report the different types of cfDNA molecules that occur in the human body based on its origin, genetic traits, and locality. We proceed by assigning existing terms to each of these cfDNA subtypes, while proposing new terms and abbreviations where clarity is lacking and more precise stratification would be beneficial. We then suggest the proper usage of these terms within different contexts and scenarios, focusing mainly on the nomenclature as it relates to the domains of oncology, prenatal testing, and post-transplant surgery surveillance. We hope that these recommendations will serve as useful considerations towards the establishment of universal cfDNA nomenclature in the future. In addition, it is conceivable that many of these recommendations can be transposed to cell-free RNA nomenclature by simply exchanging "DNA" with "RNA" in each acronym/abbreviation. Similarly, when describing DNA and RNA collectively, the suffix can be replaced with "NAs" to indicate nucleic acids.

Non-dividing Cell Virtosomes Affect In Vitro and In Vivo Tumour Cell Replication.

In vitro studies of partially purified virtosomes from rat liver showed inhibition of cell multiplication in four normal and two tumour cell lines. In vivo, the liver virtosomes slowed tumour growth and limited metastases in rats bearing DHD/K12-PROb cell initiated tumours.

The History and Future of Basic and Translational Cell-Free DNA Research at a Glance.

We discuss the early history of the structure of DNA and its involvement in gene structure as well as its mobility in and between cells and between tissues in the form of circulating cell-free DNA (cfDNA). This is followed by a view of the present status of the studies on cfDNA and clinical applications of circulating cell-free tumor DNA (ctDNA). The future developments and roles of ctDNA are also considered.

Hepatic Clearance of Cell-Free DNA: Possible Impact on Early Metastasis Diagnosis.

Circulating DNA in the bloodstream has been studied since the 1940s, leading to its identification as a possible early marker for the presence of a primary tumor. Recently, it has been more successfully employed in liquid biopsies to determine the early presence of a metastatic tumor arising after chemotherapy, radiotherapy, and surgery. The appearance of such circulating tumor DNA permits the identification of the metastatic tumor before it is detected by either palpation or radiological analysis. Nevertheless, the liquid biopsy may possibly be affected by the removal of circulating tumor DNA via the kidneys and spleen as it is released. Furthermore, the liver removal of cell-free DNA has not yet been considered to be involved in this process. Here, we review the literature on the removal of free single- and double-stranded DNA and nucleosomal, vesicular, and exosomal DNA via the liver and examine its possible impact on circulating DNA levels. The removal of all forms of DNA by the liver, together with that removed by the kidneys and spleen, may delay the timing of positive results from liquid biopsies.

Exosomes in Immune Regulation.

Exosomes, small extracellular vesicles mediate intercellular communication by transferring their cargo including DNA, RNA, proteins and lipids from cell to cell. Notably, in the immune system, they have protective functions. However in cancer, exosomes acquire new, immunosuppressive properties that cause the dysregulation of immune cells and immune escape of tumor cells supporting cancer progression and metastasis. Therefore, current investigations focus on the regulation of exosome levels for immunotherapeutic interventions. In this review, we discuss the role of exosomes in immunomodulation of lymphoid and myeloid cells, and their use as immune stimulatory agents to elicit specific cytotoxic responses against the tumor.

The virtosome-a novel cytosolic informative entity and intercellular messenger.

Studies on a range of prokaryote and eukaryote cells and tissues have shown that a newly synthesized DNA/RNA-lipoprotein complex is released in a regulated manner. This complex, termed a virtosome, is a novel cytosolic component of eukaryote cells. The released virtosomes can readily enter other cells where they can modify the biology of the recipient cells. Such modifications include immunological changes and transformation from normal to cancer cells. The virtosomes form a normal component of the circulating nucleic acids in plasma and serum currently used for clinical diagnostic purposes. Given the transformative powers of virtosomes released from tumour cells, the presence of such a complex in human plasma could readily offer the basis of an alternative mechanism for the initiation of metastases.

Predictive value of exosomes and their cargo in drug response/resistance of breast cancer patients.

Exosomes are small extracellular vesicles engaged in intercellular communication in both healthy and tumor cells. When released by the primary tumor, they transfer their cargo including nucleic acids, proteins, and lipids to target cells, thus modulating the character and fate of the recipient cells. By propagating their oncogenic content, exosomes are able to promote tumor progression, angiogenesis, metastases, and drug resistance. Their functions as delivery vehicles of biological material make exosomes promising biomarkers for the early prediction of disease progression and drug resistance in breast cancer, as well as for therapeutic targeting of molecules to treat this deadly disease. In the present review, we accentuate the relevance of exosomes as vehicles of prognostic and predictive markers and target molecules, and describe their potential therapeutic applications as drug cargo suppliers. We made an extensive literature research to clarify the association of their cargo, including exosomal DNA and RNA molecules, with the propagation of drug resistance.

Circulating Cell-Free DNA and Cancer Therapy Monitoring: Methods and Potential.

The monitoring of therapy during the treatment of cancer patients is currently assessed by the levels of circulating tumor cells or by PET/CT scans. Neither approach has the sensitivity or specificity to be very sure of the efficacy of the treatment. Moreover, PET/CT scans can be both comparatively expensive and produce low levels of radiation for the patient. The advent of the possibility of using circulating DNA released from the tumor permits (1) a possible early marker of the presence of the cancer, (2) an indication of the success of the primary treatment, (3) an indication of the early presence of possible metastasis, (4) a marker of the success of secondary subsequent treatment, (5) determining which patients can benefit from a particular treatment, and (6) offering a prognosis. These aspects will be discussed concerning the application of circulating tumor DNA analysis to the monitoring of cancer patients undergoing therapy.

MicroRNA Shuttle from Cell-To-Cell by Exosomes and Its Impact in Cancer.

The identification of exosomes, their link to multivesicular bodies and their potential role as a messenger vehicle between cancer and healthy cells opens up a new approach to the study of intercellular signaling. Furthermore, the fact that their main cargo is likely to be microRNAs (miRNAs) provides the possibility of the transfer of such molecules to control activities in the recipient cells. This review concerns a brief overview of the biogenesis of both exosomes and miRNAs together with the movement of such structures between cells. The possible roles of miRNAs in the development and progression of breast, ovarian and prostate cancers are discussed.

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer.

Ovarian cancer has a poor outcome because it is usually detected at advanced tumor stages, and the majority of the patients develop disease relapse as a result of chemotherapy resistance. This most lethal gynecological malignancy metastasizes within the peritoneal fluid or ascites to pelvic and distal organs. In ovarian cancer progression and metastasis, small non-coding RNAs (ncRNAs), including long noncoding RNAs and microRNAs have been recognized as important regulators. Their dysregulation modulates gene expression and cellular signal pathways and can be detected in liquid biopsies. In this review, we provide an overview on circulating plasma and serum ncRNAs participating in tumor cell migration and invasion, and contributing to recurrence and metastasis of ovarian cancer. We will also discuss the development of potential, novel therapies using ncRNAs as target molecules or tumor markers for ovarian cancer.

Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients.

Initially, most ovarian tumors respond to the treatment with platinum components, but frequently recurrence occurs within the following two years in advanced ovarian cancer patients. In this regard, previous studies have shown changes in the epigenetic patterns in ovarian cancer that are linked with resistance to cis- and carboplatin therapy. Thus, epigenetic changes mediated by a treatment with cis- or carboplatin could identify such patients who do or do not respond to this therapy. Therefore, an understanding of the impact of platinum on epigenetics in ovarian cancer is important in overcoming platinum resistance. In this review, we delineate epigenetic abnormalities in cis- and carboplatin-resistant ovarian tumors, such as changes in DNA methylation, histone modifications and deregulation of microRNAs, and discuss the potential of epigenetic therapies in combination with platinum.

Circulating nucleic acids in plasma and serum: applications in diagnostic techniques for noninvasive prenatal diagnosis.

The analysis of fetal nucleic acids in maternal blood 13 years ago has led to the initiation of noninvasive methods for the early determination of fetal gender, rhesus D status, and a number of aneuploid disorders and hemoglobinopathies. Subsequently, a comparatively large quantity of fetal DNA and RNA has been demonstrated in amniotic fluid as well as small amounts in premature infant saliva. The DNA and RNA in amniotic fluid has permitted an analysis of core transcriptomes, whilst the DNA and RNA in saliva allows the early detection and treatment monitoring of fetal developmental problems. These aspects are discussed together with the methodology and limits of analysis for noninvasive prenatal diagnosis in predictive, preventive, and personalized medicine.

Biology of circulating nucleic acids and possible roles in diagnosis and treatment in diabetes and cancer.

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.

Overview of healthcare in the UK.

The National Health System in the UK has evolved to become one of the largest healthcare systems in the world. At the time of writing of this review (August 2010) the UK government in its 2010 White Paper "Equity and excellence: Liberating the NHS" has announced a strategy on how it will "create a more responsive, patient-centred NHS which achieves outcomes that are among the best in the world". This review article presents an overview of the UK healthcare system as it currently stands, with emphasis on Predictive, Preventive and Personalised Medicine elements. It aims to serve as the basis for future EPMA articles to expand on and present the changes that will be implemented within the NHS in the forthcoming months.

Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer.

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.

Circulating nucleic acids in plasma and serum. Recent developments.

DNA and RNA fractions have been isolated from the whole blood, serum, plasma, the surface of blood cells, and urine of both healthy individuals and patients. The ability to isolate, quantify, and analyze these molecules has led to the identification of specific nucleic acid fragments related to particular disorders such as diabetes, cancer, myocardial infarction, and stroke, thereby permitting their early diagnosis. Currently, a number of methods for isolating the nucleic acids are employed and although a start has been made to compare the efficiencies of these methods, there is still a way to go before there are precise protocols for nucleic acid extraction. The older chemical methods of extraction still outperform some of the available kits. Some progress is being made to determine the origin of the circulating nucleic acids, although there are still many questions to be answered, including whether the source is through the spontaneous release of newly synthesized nucleic acid or whether it just derived from necrotic and apoptotic cells. In addition, it can be demonstrated that the nucleic acids can enter cells and exhibit a biological activity in the recipient cells. Hence, the question remains: Are the circulating nucleic acids freely entering tissues and cells from the blood and inducing changes in those tissues and cells? Further work is needed to elucidate these areas, and the various protocols must be standardized if the new methodology is to be widely and accurately applied in the diagnosis of disease and the monitoring of therapy. This chapter summarizes the work reported in this volume.

Metabolic DNA as the origin of spontaneously released DNA?

A DNA fraction is spontaneously released from living, but not dead or dying, human, other mammalian, avian, amphibian, plant, and prokaryote cells. The spontaneously released DNA fraction has been shown to be (a) present in both actively dividing and nondividing, differentiated cell populations; (b) labile; (c) associated with DNA-dependent RNA or DNA polymerase; (d) associated with an RNA fraction; and to have (e) a lower molecular weight than the typical genetic DNA fraction; and (f) Alu repeat sequences in increased proportions compared to a unique gene in plasma/serum. On the other hand, early autoradiographic and biochemical and quantitative cytochemical and cytophysical studies on DNA permitted the identification of a DNA fraction which was (1) present in both actively dividing and nondividing, differentiated cell populations; (2) labile; and (3) had a lower molecular weight than the typical genetic DNA fraction. This DNA fraction was termed metabolic DNA (m-DNA) and was proposed as possibly forming extra gene copies for the rapid production of m-RNA, to be destroyed subsequently. Therefore, we suggest that the metabolic DNA fraction might represent the precursor to the formation of the spontaneously released DNA fraction.

Circulating Nucleic Acids in Plasma and Serum : Proceedings of the 6th international conference on circulating nucleic acids in plasma and serum held on 9-11 November 2009 in Hong Kong.

DNA and RNA fractions have been isolated from avariety of sources including: whole blood, serum, plasma, thesurface of blood cells, urine, saliva and spinal fluid from bothhealthy individuals and patients. The ability to isolate, quantify,and analyze these molecules has led to the identification ofspecific nucleic acid fragments related to a variety of clinicaldisorders thereby permitting their early diagnosis and prognosis.This volume encompasses the proceedings of the 6th internationalconference on circulating nucleic acids in plasma and serum heldfrom the 9th to the 11th of November 2009 in Hong Kong. The topicsthat are covered in these proceedings include: - Nucleic Acids inOncology - Nucleic Acids in Foetal Medicine - The Biology of CNAPS- New Technologies for CNAPS - Other Clinical Exploitation ofCNAPS

Messenger DNA in higher plants.

Evidence is presented that, as in animal and human cells, plant cells can release a newly-synthesized DNA which can freely circulate in the plants. This DNA enters cells and their nuclei where it may be integrated and be expressed so acting, apparently, as a messenger-DNA.