1,721,163 research outputs found
NEW PERSPECTIVE IN PROSTATE CANCER DIAGNOSIS AND TREATMENT: A PIVOTAL STUDY ON EEF1A1 PROTEIN LEVELS AS POTENTIAL THERAPEUTIC TARGET AND LIQUID BIOPSY ON CFDNA OF EEF1A1, CFRNA EEF1A1 AND CFDI OF LINE-1 AS NEW DIAGNOSTIC AND PROGNOSTIC BIOMARKERS
Full text linkThe overall aim of our project was the further development and validation in real settings of the highly sensitive and quantitative diagnostic platform digital droplet PCR for the early and fast detection of plasma cfDNA quantity and cfDI of repetitive elements, such as LINE-1, associated to prostate cancer. This non-invasive blood test could serve to better define the diagnosis, identifying high risk PCa patients. If validated, the test could enter the clinical practice, reducing the need of patient’s biopsy and, thus, health care costs and patients’ suffering. Moreover, the test could have the potential to be develop as a screening method or as a test for the molecular stratification of patients in the follow-up.
Secondary endpoint: evaluate the diagnostic and prognostic value of liquid biopsy of biomarkers like eEF1A1 e eEF1A2. The rationale is that the research group has demonstrated the role of eEF1A2 and eEF1A1 in onset and progression, respectively, of prostate cancer. These two targets have been studied at DNA and mRNA levels in plasma circulating nucleic acids and in tissues.
Materials and Methods
The study was approved by the Ethical Committee of the UNITS (n.102, 16.01.20 and n.110 25.01.21). We enrolled a preliminary pool of patients from our hospital with a suspected PCa undergoing a prostate biopsy. Through a blood sample, we tested a specific cfDNA LINE-1, to demonstrate if these repetitive elements can be related to the diagnosis and staging of PCa. The plasma was than prepared and anonymously preserved in a blood bank at our Institute following the method set up by the research group. After the anatomopathological diagnosis of the biopsy, samples of 41 plasma of cancer patients (cases) and 19 plasma of negative cancer patients (controls) were selected for the explorative analysis. The circulating cfDNA/cfRNA were extracted by QIAamp ccfDNA/RNA Kit and stocked into dedicated cryovials in a bank at -80°C. The LINE-1 target in cfDNA were detected by ddPCR technology using Eva Green assays. The cfDNA integrity (cfDI) was obtained from the ratio of longer/shorter fragments following the method set up by the research group. The EEF1A1/A2 DNA and the cDNA of eEF1A1 were evaluated by FAM/HEX probe assays. The EEF1A1/A2 DNA copies, the cDNA of eEF1A1 and cfDI of LINE-1 were compared between cases and controls by statistical evaluation.
Results
Higher eEF1A1 expression in Gleason 7–8 tissues vs Gleason 4–6 tissues (Gleason ≥ 7, 87% vs. Gleason ≤ 6, 54%; p = 0.033). Patients exhibiting elevated eEF1A1 expression experienced poorer clinical outcomes. To highlight the role of eEF1A1 in aggressive PCa, we used a cell model. In PC-3 hormone-independent cancer cells, but not in non-tumorigenic PZHPV-7 cells, GT75 led to reduced cell viability, increased autophagy, and enhanced cell detachment. Remarkably, in PC-3 cells, GT75 primarily co-localized with the fraction of eEF1A1 bound to actin. Elevated eEF1A1 protein levels could serve as an indicator of aggressive prostate cancer forms. Moreover, targeting eEF1A1 with GT75 impaired cell viability specifically in PC-3 cancer cells but had no effect on PZHPV-7 non- tumorigenic cells, suggesting a distinct role for this protein in cancer cell survival. Preliminary analysis of plasma liquid biopsy data revealed no significant differences between cases and controls in the EEF1A1/EEF1A2 DNA copy ratio. The presence of mRNA from eEF1A1 was the only evaluable variable and no difference was found between cases and controls. In contrast, the cfDI of LINE -1 showed a significant difference between cases and controls, with the cfDI of LINE -1 being lower in cases than in controls (Mann-Whitney test p=0.004). The amount of cfDNA measured by EEF1A1 or EEF1A2 was also higher in cases than controls (Mann-Whitney test p=0.04). The cfDI of LIN the cfDI of LINE -1 in plasma can distinguish cases of prostate cancer from healthy controls.The overall aim of our project was the further development and validation in real settings of the highly sensitive and quantitative diagnostic platform digital droplet PCR for the early and fast detection of plasma cfDNA quantity and cfDI of repetitive elements, such as LINE-1, associated to prostate cancer. This non-invasive blood test could serve to better define the diagnosis, identifying high risk PCa patients. If validated, the test could enter the clinical practice, reducing the need of patient’s biopsy and, thus, health care costs and patients’ suffering. Moreover, the test could have the potential to be develop as a screening method or as a test for the molecular stratification of patients in the follow-up.
Secondary endpoint: evaluate the diagnostic and prognostic value of liquid biopsy of biomarkers like eEF1A1 e eEF1A2. The rationale is that the research group has demonstrated the role of eEF1A2 and eEF1A1 in onset and progression, respectively, of prostate cancer. These two targets have been studied at DNA and mRNA levels in plasma circulating nucleic acids and in tissues.
Materials and Methods
The study was approved by the Ethical Committee of the UNITS (n.102, 16.01.20 and n.110 25.01.21). We enrolled a preliminary pool of patients from our hospital with a suspected PCa undergoing a prostate biopsy. Through a blood sample, we tested a specific cfDNA LINE-1, to demonstrate if these repetitive elements can be related to the diagnosis and staging of PCa. The plasma was than prepared and anonymously preserved in a blood bank at our Institute following the method set up by the research group. After the anatomopathological diagnosis of the biopsy, samples of 41 plasma of cancer patients (cases) and 19 plasma of negative cancer patients (controls) were selected for the explorative analysis. The circulating cfDNA/cfRNA were extracted by QIAamp ccfDNA/RNA Kit and stocked into dedicated cryovials in a bank at -80°C. The LINE-1 target in cfDNA were detected by ddPCR technology using Eva Green assays. The cfDNA integrity (cfDI) was obtained from the ratio of longer/shorter fragments following the method set up by the research group. The EEF1A1/A2 DNA and the cDNA of eEF1A1 were evaluated by FAM/HEX probe assays. The EEF1A1/A2 DNA copies, the cDNA of eEF1A1 and cfDI of LINE-1 were compared between cases and controls by statistical evaluation.
Results
Higher eEF1A1 expression in Gleason 7–8 tissues vs Gleason 4–6 tissues (Gleason ≥ 7, 87% vs. Gleason ≤ 6, 54%; p = 0.033). Patients exhibiting elevated eEF1A1 expression experienced poorer clinical outcomes. To highlight the role of eEF1A1 in aggressive PCa, we used a cell model. In PC-3 hormone-independent cancer cells, but not in non-tumorigenic PZHPV-7 cells, GT75 led to reduced cell viability, increased autophagy, and enhanced cell detachment. Remarkably, in PC-3 cells, GT75 primarily co-localized with the fraction of eEF1A1 bound to actin. Elevated eEF1A1 protein levels could serve as an indicator of aggressive prostate cancer forms. Moreover, targeting eEF1A1 with GT75 impaired cell viability specifically in PC-3 cancer cells but had no effect on PZHPV-7 non- tumorigenic cells, suggesting a distinct role for this protein in cancer cell survival. Preliminary analysis of plasma liquid biopsy data revealed no significant differences between cases and controls in the EEF1A1/EEF1A2 DNA copy ratio. The presence of mRNA from eEF1A1 was the only evaluable variable and no difference was found between cases and controls. In contrast, the cfDI of LINE -1 showed a significant difference between cases and controls, with the cfDI of LINE -1 being lower in cases than in controls (Mann-Whitney test p=0.004). The amount of cfDNA measured by EEF1A1 or EEF1A2 was also higher in cases than controls (Mann-Whitney test p=0.04). The cfDI of LIN the cfDI of LINE -1 in plasma can distinguish cases of prostate cancer from healthy controls
Finding the Wolf in Sheep's Clothing: The 4Kscore Is a Novel Blood Test That Can Accurately Identify the Risk of Aggressive Prostate Cancer
Full text linkBetter biomarkers that can discriminate between aggressive and indolent phenotypes of prostate cancer are urgently needed. In the first 20 years of the prostate-specific antigen (PSA) era, screening for prostate cancer has successfully reduced prostate cancer mortality, but has led to significant problems with overdiagnosis and overtreatment. As a result, many men are subjected to unnecessary prostate biopsies and overtreatment of indolent cancer in order to save one man from dying of prostate cancer. A novel blood test known as the 4Kscore® Test (OPKO Lab, Nashville, TN) incorporates a panel of four kallikrein protein biomarkers (total PSA, free PSA, intact PSA, and human kallikrein-related peptidase 2) and other clinical information in an algorithm that provides a percent risk for a high-grade (Gleason score ≥ 7) cancer on biopsy. In 10 peer-reviewed publications, the four kallikrein biomarkers and algorithm of the 4Kscore Test have been shown to improve the prediction not only of biopsy histopathology, but also surgical pathology and occurrence of aggressive, metastatic disease. Recently, a blinded prospective trial of the 4Kscore Test was conducted across the United States among 1012 men. The 4Kscore Test replicated previous European results showing accuracy in predicting biopsy outcome of Gleason score ≥ 7. In a recent case-control study nested within a population-based cohort from Västerbotten, Sweden, the four kallikrein biomarkers of the 4Kscore Test also predicted the risk for aggressive prostate cancer that metastasized within 20 years after the test was administered. These results indicate that men with an abnormal PSA or digital rectal examination result, and for whom an initial or repeat prostate biopsy is being considered, would benefit from a reflex 4Kscore Test to add important information to the clinical decision-making process. A high-risk 4Kscore Test result may be used to select men with a high probability of aggressive prostate cancer who would benefit from a biopsy of the prostate to prevent an adverse and potentially lethal outcome from prostate cancer. Men with a low 4Kscore Test result may safely defer biopsy
Human immunodeficiency virus and sexually transmitted disease disparities among transgender persons
Full text linkExperiencies of transphobic discrimination and victimization negatively impact on mental health, and the lack of social support has been found to be associated with a higher rate of undiagnosed HIV infection. To accurately assess the prevalence of HIV infection and other sexually transmitted diseases in the transgender population it is essential to create centres that can offer a comprehensive, multidisciplinary and adequate support to these patients
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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