1,720,974 research outputs found
Clinical implications of extracellular vesicles in prostate and breast cancer
Full text linkExtracellular vesicles (EVs) are small membrane-derived particles released in physiological and also pathological conditions. EVs can be found in different body fluids, such as blood, urine and saliva, but also into extracellular space of all cell types. EVs carry several biological and genetic information leading to recognition of them as important mediators for cellular communication from
donor to recipient cells. Recent evidence has shown the clinical implication of EVs, in particular of small vesicles, called exosomes, as good candidates for investigation of biomarkers associated with cancer diagnosis, prognosis, monitoring and therapy decision.
Prostate cancer (PCa) is the most frequently diagnosed cancer in the elderly population. The serum prostate-specific antigen (PSA) level is the gold standard biomarkers used for the PCa early diagnosis. However, PSA test alone results not sufficiently specific and, consequently, gives false positive samples who need an invasive useless bioptic evaluation, leading to the need of a more accurate biomarkers research.
Breast cancer (BC) is the most frequently diagnosed female cancer. BC relapse occurs in the first 5 years after diagnosis in patients with hormone receptor-positive BC. Systemic recurrence is due to the presence of the minimal residual disease (MRD) after surgery or present at initial diagnosis, but undetectable by imaging or conventional blood tests. Putative biomarkers able to detect MRD using non-invasive approaches can allow the monitoring of tumor evolution, providing prognostic information and guiding therapeutic decisions.
The analysis and the characterisation of prostate and breast tumor-related EVs was performed aiming at finding their potential clinical implications. Different isolation methods were tested to obtain a high quantity and quality EVs from several body fluids (serum and urinary supernatant).
Prostate cancer EVs were investigated aiming to find an early diagnostic role. In particular, EVs isolated from sera and urine of 10 PCa patients, 10 BPH patients and 10 healthy individuals, were phenotypically and morphologically characterised using MACSPlex kit, which allows simultaneous analysis of 37 surface epitopes, and transmission electron microscopy (TEM), respectively. We found a different significant expressions of surface exosome-related proteins in EVs from serum (CD62P, CD41b, CD42a, CD29, CD31) and from urinary supernatant (CD9, CD63, CD24) of PCa patients, BPH patients and healthy donors. TEM analysis showed no difference in terms of shape and size of EVs among the various conditions.
Breast cancer EVs were investigated for their miRNA cargo as potential monitoring MRD markers after surgery. In particular, EVs were isolated from sera of 12 BC patients, which were
collected after 6 months from the surgery, and of 11 healthy individuals. Exosomal miRNAs were extracted and a small RNA Seq approach was performed.
After raw data elaboration and normalization, 52 exosomal miRNAs were found to be significantly differentially expressed between BC and H, suggesting a putative role of this miRNA pattern as BC-related markers and for MRD detection. Several exosomal miRNA have been already shown as correlated with BC but also with other cancer types (i.e. miR-148a-3p, miR-221-3p, miR-16-5p, miR-15a-5p, miR-25-3p). Other miRNAs are involved in pathways, such as Wnt and mTOR/PI3K/Akt, in cell cycle, TNF, Ras, p53 signalling.
In conclusion, our results suggest the potential clinical application of EVs analysis in prostate and breast cancer as good non-invasive and informative biomarkers
Know your enemy: Genetics, aging, exposomic and inflammation in the war against triple negative breast cancer.
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Urinary Cell-Free DNA: Potential and Applications
No full textUrine could be a convenient source of biomarkers for different diseases and clinical applications, mostly for cancer diagnosis, prognosis, treatment monitoring, and prenatal diagnosis. The ultra-noninvasive sampling and the possibility to analyze large volume are the main undisputed advantages of urine-based protocols. Recent and comprehensive studies showed that urinary cell-free DNA (ucfDNA) is informative to identify the genomic signature of patients, resulting in a huge tool to track the tumor evolution and for personalized medicine in urological and non-urological cancer.In this chapter, we reported the main published evidences on ucfDNA, with the aim at discussing its promising and translatable role in clinical practices
Urinary Cell-Free DNA: Isolation, Quantification, and Quality Assessment
No full textUrine cell-free DNA is an important source of diagnostic markers for different diseases (e.g., cancer and prenatal diagnosis). It is important to achieve a simple and fast protocol to maximize the recovery of DNA from urine supernatant and to assess its quality. Here we describe a simple approach from urine collection to DNA quality assessment for downstream analyses
Studying Copy Number Variations in Cell-Free DNA: The Example of AR in Prostate Cancer
No full textSerum and plasma cell-free DNA (cfDNA) has been shown as an informative noninvasive source of biomarkers for different diseases, including cancer. Starting from the hypothesis that the gain of androgen receptor (AR) gene is a frequent aberration in advanced prostate cancer patients, we analyzed it in cfDNA as a potential predictive biomarker of specific treatments. Here we report a general protocol that may be considered to analyze gene copy number variations in serum or plasma fluids
Androgen receptor in breast cancer: A wolf in sheep's clothing? A lesson from prostate cancer
No full textThe possibility that a receptor for androgen is expressed in Breast Cancer (BC) is fascinating given that the tumor is predominantly estrogen-dependent. The androgen receptor (AR) is emerging as a new marker and a potential new therapeutic target in the treatment of BC patients. The recent availability of selective AR inhibitors (e.g. bicalutamide, enzalutamide, apalutamide) approved for the treatment of prostate cancer has opened up the possibility to use them in BC patients whose tumors express AR. However, AR appears to have various functions according to the BC subtype, e.g. ER-positive or triple negative BC and the patient prognosis is different on the basis of the presence or absence of estrogen and progesterone receptors. Moreover, a different AR expression was seen according to the various ethnicities. Of note, in population at low economical income, the availability of anti-AR compounds at low cost could open the possibility to treat AR-positive triple negative BC that are highly present in these populations. Up to now, AR detection is not routinely performed in BC. The standardization of AR detection methods could render AR an easily detectable marker in primary BC and metastatic samples. Nevertheless, the overall concordance of 60% of AR expression in primary tumor and metastasis implies that a clinician who need the AR value to give anti-AR therapy should have the data on both the tumor materials. Following the comprehensive studies on prostate cancer the possibility to test AR on liquid biopsies suggest the use of this biomarker for a real-time disease monitoring. Finally, considering the possibility to treat patients with immune checkpoint inhibitors there is the need to know the relation between microenvironment and AR in BC
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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