scholarly journals COVID-19 engages clinical markers for the management of cancer and cancer-relevant regulators of cell proliferation, death, migration, and immune response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Serhiy Souchelnytskyi ◽  
Andriy Nera ◽  
Nazariy Souchelnytskyi
Keyword(s):  
Cell Proliferation ◽  
Immune System ◽  
Cancer Patients ◽  
Tumor Suppressors ◽  
Evidence Based ◽  
Biological Processes ◽  
Clinical Markers ◽  
Clinical Observations ◽  
Potential Impact ◽  
Selection Of

AbstractClinical reports show that the management of cancer patients infected with SARS-CoV-2 requires modifications. Understanding of cancer-relevant mechanisms engaged by the virus is essential for the evidence-based management of cancer. The network of SARS-CoV-2 regulatory mechanisms was used to study potential engagement of oncogenes, tumor suppressors, other regulators of tumorigenesis and clinical markers used in the management of cancer patients. Our network analysis confirms links between COVID-19 and tumorigenesis that were predicted in epidemiological reports. The COVID-19 network shows the involvement of tumorigenesis regulators and clinical markers. Regulators of cell proliferation, death, migration, and the immune system were retrieved. Examples are pathways initiated by EGF, VEGF, TGFβ and FGF. The SARS-CoV-2 network engages markers for diagnosis, prognosis and selection of treatment. Intersection with cancer diagnostic signatures supports a potential impact of the virus on tumorigenesis. Clinical observations show the diversity of symptoms correlating with biological processes and types of cells engaged by the virus, e.g. epithelial, endothelial, smooth muscle, glial and immune system cells. Our results describe an extensive engagement of cancer-relevant mechanisms and clinical markers by COVID-19. Engagement by the virus of clinical markers provides a rationale for clinical decisions based on these markers.

Molecular testing guidelines for selection of colorectal cancer patients for targeted and conventional therapies.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 600-600
Author(s):  
Antonia R. Sepulveda ◽  
Stanley R. Hamilton ◽  
Wayne Grody
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Molecular Testing ◽  
Evidence Based ◽  
Biomarker Testing ◽  
Crc Management ◽  
Colorectal Cancer Patients ◽  
Evidence Based Guidelines ◽  
Selection Of

600 Background: Molecular testing to enhance the response of colorectal cancers (CRC) to targeted and conventional therapies has been the center of many recent studies. While testing for KRAS mutations is generally accepted as a requirement to select patients for anti-EGFR antibody therapies, evidence-based guidelines for other markers are needed. The objective of this project is to establish evidence-based recommendations for the molecular testing of CRC tissues to guide EGFR-targeted therapies and conventional chemotherapy regimens. Methods: Three professional societies: American Society of Clinical Pathologists (ASCP), College of American Pathologists (CAP) and the Association for Molecular Pathology (AMP) have selected co-chairs, and multidisciplinary expert and advisory panels, which include specialists in pathology, GI oncology, surgery, gastroenterology and genetics. A systematic review was designed based on five overall key questions: (1) What biomarkers are useful for CRC management (selection of patients for targeted and conventional therapies)? (2) How should tissue specimens be processed for biomarker testing for CRC management?; (3) How should biomarker testing for CRC management be performed? (4) How should molecular testing of CRC be implemented and operationalized?; V: Should other genes/biomarkers be routinely tested? The expert panel will review title-abstract (TA) and full-text (FT) in DistillerSR software. Data extraction will then be performed and the panel will draft recommendations based upon evidence tables and the considered judgment process. Results: A systematic review was performed to capture published articles from January 2009 through August 2013, yielding 2,883titles to date. Currently the TA review phase is in course. Release of draft recommendations during an open comment period is anticipated in early 2014. Conclusions: The ASCP-CAP-AMP Molecular Testing Guidelines for Selection of Colorectal Cancer Patients for Targeted and Conventional Therapies will provide evidence-based guidelines for molecular testing of CRC. The final publication release is anticipated for the fall 2014.

An Insight into Oligopeptide Transporter 3 (OPT3) family proteins

2020 ◽  
Vol 27 ◽  
Author(s):  
Fırat Kurt
Keyword(s):  
Stress Responses ◽  
Chelating Agent ◽  
Biological Processes ◽  
Biotic And Abiotic Stress ◽  
Oligopeptide Transporter ◽  
Binding Residues ◽  
Fe Homeostasis ◽  
Proteins Interactions ◽  
Insight Into ◽  
Selection Of

: Oligopeptide transporter 3 (OPT3) proteins are one of the subsets of OPT clade, yet little is known about these transporters. Therefore, homolog OPT3 proteins in several plant species were investigated and characterized using bioinformatical tools. Motif and co-expression analyses showed that OPT3 proteins may be involved in both biotic and abiotic stress responses as well as growth and developmental processes. AtOPT3 usually seemed to take part in Fe homeostasis whereas ZmOPT3 putatively interacted with proteins involved in various biological processes from plant defense system to stress responses. Glutathione (GSH), as a putative alternative chelating agent, was used in the AtOPT3 and ZmOPT3 docking analyses to identify their putative binding residues. The information given in this study will contribute to the understanding of OPT3 proteins’ interactions in various pathways and to the selection of potential ligands for OPT3s.

Immune System Alterations by Aldosterone During Hypertension: From Clinical Observations to Genomic and Non-Genomic Mechanisms Leading to Vascular Damage

2013 ◽  
Vol 13 (6) ◽  
pp. 1035-1046 ◽  
Author(s):  
N. Munoz-Durango ◽  
M.F. Barake ◽  
N.A. Letelier ◽  
C. Campino ◽  
C.E. Fardella ◽  
...  
Keyword(s):  
Immune System ◽  
Vascular Damage ◽  
Clinical Observations

Evidence-based Assessment

2010 ◽  
pp. 76-98
Author(s):  
John Hunsley ◽  
Eric J. Mash
Keyword(s):  
Decision Making ◽  
Clinical Assessment ◽  
Assessment Process ◽  
Evidence Based ◽  
The Past ◽  
Specific Assessment ◽  
The Many ◽  
Selection Of ◽  
Made In

Evidence-based assessment relies on research and theory to inform the selection of constructs to be assessed for a specific assessment purpose, the methods and measures to be used in the assessment, and the manner in which the assessment process unfolds. An evidence-based approach to clinical assessment necessitates the recognition that, even when evidence-based instruments are used, the assessment process is a decision-making task in which hypotheses must be iteratively formulated and tested. In this chapter, we review (a) the progress that has been made in developing an evidence-based approach to clinical assessment in the past decade and (b) the many challenges that lie ahead if clinical assessment is to be truly evidence-based.

scholarly journals Incorporating radiomics into clinical trials: expert consensus on considerations for data-driven compared to biologically driven quantitative biomarkers

2021 ◽  
Author(s):  
Laure Fournier ◽  
Lena Costaridou ◽  
Luc Bidaut ◽  
Nicolas Michoux ◽  
Frederic E. Lecouvet ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Quantitative Imaging ◽  
A Priori ◽  
External Validation ◽  
Data Driven ◽  
Imaging Biomarkers ◽  
Clinical Validation ◽  
Biological Processes ◽  
Imaging Data ◽  
Selection Of

Abstract Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

scholarly journals Azathioprine immunosuppression and disease modification in Parkinson’s disease (AZA-PD): a randomised double-blind placebo-controlled phase II trial protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040527
Author(s):  
Julia C Greenland ◽  
Emma Cutting ◽  
Sonakshi Kadyan ◽  
Simon Bond ◽  
Anita Chhabra ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Phase Ii ◽  
Rating Scale ◽  
Positron Emission Tomography Imaging ◽  
Clinical Markers ◽  
Double Blind ◽  
Positron Emission ◽  
Immunosuppressant Medication

IntroductionThe immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.Methods and analysisAZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.Ethics and disseminationThe study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.Trial registration numbersISRCTN14616801 and EudraCT- 2018-003089-14.

scholarly journals Tetracycline-Resistant Bacteria Selected from Water and Zebrafish after Antibiotic Exposure

2021 ◽  
Vol 18 (6) ◽  
pp. 3218
Author(s):  
Ana Rita Almeida ◽  
Marta Tacão ◽  
Joana Soares ◽  
Inês Domingues ◽  
Isabel Henriques
Keyword(s):  
Statistical Significance ◽  
Recovery Period ◽  
Antibiotic Resistance Genes ◽  
Antibiotic Use ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Potential Impact ◽  
Susceptibility Profiles ◽  
Selection Of ◽  
Significant Mortality

The emergence of antibiotic-resistant pathogens due to worldwide antibiotic use is raising concern in several settings, including aquaculture. In this work, the selection of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) was evaluated after exposure of zebrafish to oxytetracycline (OTC) for two months, followed by a recovery period. The selection of ARB in water and fish was determined using selective media. The abundance of tetA genes was estimated through qPCR. Higher prevalence of ARB was measured in all samples exposed to the antibiotic when compared to control samples, although statistical significance was only achieved five days after exposure. Isolates recovered from samples exposed to the antibiotic were affiliated with Pseudomonas and Stenotrophomonas. Various antibiotic susceptibility profiles were detected and 37% of the isolates displayed multidrug resistance (MDR). The selection of the tetA gene was confirmed by qPCR at the highest OTC concentration tested. Two MDR isolates, tested using zebrafish embryos, caused significant mortality, indicating a potential impact on fish health and survival. Overall, our work highlights the potential impact of antibiotic contamination in the selection of potential pathogenic ARB and ARGS.

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