scholarly journals Transcriptional analysis identifies novel biomarkers associated with successful ex-vivo perfusion of human donor lungs

2019 ◽  
Author(s):  
John R. Ferdinand ◽  
Morvern I. Morrison ◽  
Anders Andreasson ◽  
Catriona Charlton ◽  
Alisha Chhatwal ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Ex Vivo ◽  
Clinical Decision ◽  
Transcriptional Analysis ◽  
Organ Shortage ◽  
Gene Encoding ◽  
Human Donor ◽  
Club Cell ◽  
Protein Levels ◽  
Novel Biomarkers

AbstractTransplantation is an effective treatment for end-stage lung disease but donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of marginal organs enables functional assessment under normothermic conditions to facilitate clinical decision-making around utilisation, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remains to be determined. Here we used RNA sequencing to delineate changes in gene expression occurring in n=10 donor lungs undergoing EVLP, comparing lungs that were deemed transplantable (n=6) to those deemed unusable (n=4). We found that lungs deemed suitable for transplantation following EVLP had reduced induction of a number of innate immune pathways during EVLP, but a greater increase in genes involved in oxidative phosphorylation, a critical ATP-degenerating pathway. Furthermore, SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes were significantly increased in transplantable lungs following perfusion, whilst CHIT-1 was decreased. Using a larger validation cohort (n=18), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable and non-transplantable lungs (AUC 0.81). Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may amenable to therapeutic intervention during EVLP.Single sentence summaryTranscriptional changes in lungs undergoing ex vivo normothermic perfusion identify chitinase1 and club cell genes as potential biomarkers to guide utilisation

scholarly journals Transcriptional analysis identifies potential novel biomarkers associated with successful ex‐vivo perfusion of human donor lungs

2021 ◽  
Author(s):  
John Robert Ferdinand ◽  
Morvern Isabel. Morrison ◽  
Anders Andreasson ◽  
Catriona Charlton ◽  
Alisha Kaur Chhatwal ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Transcriptional Analysis ◽  
Human Donor ◽  
Ex Vivo Perfusion ◽  
Novel Biomarkers

scholarly journals Elucidation of tumor-stromal heterogeneity and the ligand-receptor interactome by single cell transcriptomics in real-world pancreatic cancer biopsies

2020 ◽  
Author(s):  
Jaewon Lee ◽  
Vincent Bernard ◽  
Alexander Semaan ◽  
Maria Monberg ◽  
Jonathan Huang ◽  
...  
Keyword(s):  
Single Cell ◽  
Clinical Decision Making ◽  
De Novo ◽  
Ex Vivo ◽  
Clinical Decision ◽  
Ductal Adenocarcinoma ◽  
Cancer Associated Fibroblast ◽  
Parental Tumor

Abstract Precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC) are imperative for improving disease outcomes. However, the long-term fidelity of recently deployed ex vivo preclinical platforms, such as patient-derived organoids (PDOs), remains unknown. Through single-cell RNA sequencing (scRNA-seq), we identify substantial transcriptomic evolution of PDOs propagated from the parental tumor, which may alter predicted drug sensitivity. In contrast, scRNA-seq is readily applicable to limited biopsies from human primary and metastatic PDAC and identifies most cancers as being an admixture of previously described epithelial transcriptomic subtypes. Integrative analyses of our data provide an in-depth characterization of the heterogeneity within the tumor microenvironment, including cancer-associated fibroblast (CAF) subclasses, and predict a multitude of ligand-receptor interactions, revealing potential targets for immunotherapy approaches. While PDOs continue to enable prospective therapeutic prediction, our analysis also demonstrates the complementarity of using orthogonal de novo biopsies from PDAC patients paired with scRNA-seq to inform clinical decision-making.

scholarly journals Serum circular RNAs act as blood-based biomarkers for hypertrophic obstructive cardiomyopathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kristina Sonnenschein ◽  
Adriana Luisa Wilczek ◽  
David de Gonzalo-Calvo ◽  
Angelika Pfanne ◽  
Anselm Arthur Derda ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Clinical Decision Making ◽  
Heart Diseases ◽  
Expression Patterns ◽  
Clinical Decision ◽  
Hypertrophic Obstructive Cardiomyopathy ◽  
Circular Rnas ◽  
Inverse Association ◽  
Echocardiographic Parameters ◽  
Novel Biomarkers

AbstractHypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and is associated with a high risk of sudden cardiac death. HCM is characterized by pronounced hypertrophy of cardiomyocytes, fiber disarray and development of fibrosis and can be divided into a non-obstructive (HNCM) and obstructive form (HOCM) therefore requiring personalized therapeutic therapies. In the present study, we investigated the expression patterns of several circulating circular RNAs (circRNAs) as potential biomarkers in patients with HCM. We included 64 patients with HCM and 53 healthy controls to the study and quantitatively measured the expression of a set of circRNAs already known to be associated with cardiac diseases (circDNAJC6) and/or being highly abundant in blood (circTMEM56 and circMBOAT2). Abundancy of circRNAs was then correlated to relevant clinical parameters. Serum expression levels of circRNAs DNAJC6, TMEM56 and MBOAT2 were downregulated in patients with HCM. The inverse association between circRNA levels and HCM remained unchanged even after adjusting for confounding factors. All circRNAs, evaluated separately or in combination, showed a robust discrimination capacity when comparing control subjects with HCM, HNCM or HOCM patients (AUC from 0.722 to 0.949). Two circRNAs, circTMEM56 and circDNAJC6, significantly negatively correlated with echocardiographic parameters for HOCM. Collectively, circulating circRNAs DNAJC6, TMEM56 and MBOAT2 can distinguish between healthy and HCM patients. In addition, circTMEM56 and circDNAJC6 could serve as indicators of disease severity in patients with HOCM. Thus, circRNAs emerge as novel biomarkers for HCM facilitating the clinical decision making in a personalized manner.

Investigation of the effects of two-, four-, six- and eight-strand suture repairs on the biomechanical properties of canine gastrocnemius tenorrhaphy constructs

2021 ◽  
pp. 1-7
Author(s):  
Yi-Jen Chang ◽  
Daniel J. Duffy ◽  
George E. Moore
Keyword(s):  
Failure Modes ◽  
Clinical Decision Making ◽  
Ex Vivo ◽  
Biomechanical Testing ◽  
Tendon Repair ◽  
Clinical Decision ◽  
Biomechanical Properties ◽  
Suture Technique ◽  
Gap Formation ◽  
Ex Vivo Model

Abstract OBJECTIVE To determine the effects of 2-, 4-, 6- and 8-strand suture repairs on the biomechanical properties of canine gastrocnemius tenorrhaphy constructs in an ex vivo model. SAMPLE 56 cadaveric gastrocnemius musculotendinous units from 28 adult large-breed dogs. PROCEDURES Tendons were randomly assigned to 4 repair groups (2-, 4-, 6- or 8-strand suture technique; n = 14/group). Following tenotomy, repairs were performed with the assigned number of strands of 2-0 polypropylene suture in a simple interrupted pattern. Biomechanical testing was performed. Yield, peak, and failure loads, the incidence of 1- and 3-mm gap formation, forces associated with gap formation, and failure modes were compared among groups. RESULTS Yield, peak, and failure forces differed significantly among groups, with significantly greater force required as the number of suture strands used for tendon repair increased. The force required to create a 1- or 3-mm gap between tendon ends also differed among groups and increased significantly with number of strands used. All constructs failed by mode of suture pull-through. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that increasing the number of suture strands crossing the repair site significantly increases the tensile strength of canine gastrocnemius tendon repair constructs and their resistance to gap formation. Future studies are needed to assess the effects of multistrand suture patterns on tendon glide function, blood supply, healing, and long-term clinical function in dogs to inform clinical decision-making.

scholarly journals Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4214
Author(s):  
Sutpirat Moonmuang ◽  
Parunya Chaiyawat ◽  
Salinee Jantrapirom ◽  
Dumnoensun Pruksakorn ◽  
Luca Lo Piccolo
Keyword(s):  
Clinical Decision Making ◽  
Expression Patterns ◽  
Osteogenic Sarcoma ◽  
Clinical Decision ◽  
Diagnostic Tools ◽  
Liquid Biopsies ◽  
Specific Expression ◽  
Altered Expression ◽  
Novel Biomarkers ◽  
Non Coding Rnas

Circulating cell-free nucleic acids recently became attractive targets to develop non-invasive diagnostic tools for cancer detection. Along with DNA and mRNAs, transcripts lacking coding potential (non-coding RNAs, ncRNAs) directly involved in the process of tumor pathogenesis have been recently detected in liquid biopsies. Interestingly, circulating ncRNAs exhibit specific expression patterns associated with cancer and suggest their role as novel biomarkers. However, the potential of circulating long ncRNAs (c-lncRNAs) to be markers in osteosarcoma (OS) is still elusive. In this study we performed a systematic review to identify thirteen c-lncRNAs whose altered expression in blood associate with OS. We herein discuss the potential impact that these c-lncRNAs may have on clinical decision-making in the management of OS. Overall, we aimed to provide novel insights that can contribute to the development of future precision medicine in oncology.

scholarly journals Exosomes in Nephropathies: A Rich Source of Novel Biomarkers

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Christos Masaoutis ◽  
Samer Al Besher ◽  
Ioannis Koutroulis ◽  
Stamatios Theocharis
Keyword(s):  
Kidney Disease ◽  
Clinical Decision Making ◽  
Cell Communication ◽  
Clinical Decision ◽  
Rich Source ◽  
Diagnostic Tools ◽  
Renal Diseases ◽  
Disease Biomarkers ◽  
Novel Biomarkers ◽  
Low Sensitivity

The biomarkers commonly utilized in diagnostic evaluations of kidney disease suffer from low sensitivity, especially in the early stages of renal damage. On the other hand, obtaining a renal biopsy to augment clinical decision making can lead to potentially serious complications. In order to overcome the shortcomings of currently available diagnostic tools, recent studies suggest that exosomes, cell-secreted extracellular vesicles containing a large array of active molecules to facilitate cell-to-cell communication, may represent a rich source of novel disease biomarkers. Because of their endocytic origin, exosomes carry markers typical for their parent cells, which could permit the localization of biochemical cellular alterations in specific kidney compartments. Different types of exosomes can be isolated from noninvasively obtained biofluids; however, in the context of kidney disease, evidence has emerged on the role of urinary exosomes in the diagnostic and predictive modeling of renal pathology. The current review summarizes the potential application of exosomes in the detection of acute and chronic inflammatory, metabolic, degenerative, and genetic renal diseases.

Novel live tumor cell diagnostic test utilizing biophysical and molecular biomarkers to assess local, advanced, and metastatic prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 211-211
Author(s):  
Kevin B. Knopf ◽  
Michael S. Manak ◽  
Wendell R. Su ◽  
Thiagarajan Meyyappan ◽  
Andrew Min ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Machine Vision ◽  
Tumor Cells ◽  
Diagnostic Test ◽  
Clinical Decision Making ◽  
Ex Vivo ◽  
Metastatic Potential ◽  
Clinical Decision ◽  
High Risk Prostate Cancer

211 Background: Over-treatment of prostate cancer affects 144,000 patients annually in the U.S. due to the inaccuracy of current diagnostics for risk stratification. Functional molecular and biophysical biomarkers combined with clinically actionable diagnostic platforms are used for evaluating the local invasiveness and metastatic potential of cells derived from biopsy. Such a diagnostic test may improve patient outcomes in low-to high-risk prostate cancers according to D’Amico’s definition. This study describes the development of a novel phenotypic diagnostic using a set of biomarkers measured with a proprietary live cell assay coupled with innovative machine vision algorithms for patient tumor samples using a unique microfluidic platform. Methods: We assessed 60 prostate cancer samples collected post radical prostatectomy (RP). We report the assay details for culturing live tumor cells ex vivo, enabling automated imaging of phenotypic biomarkers. The test is designed to sustain survival of prostate tumor cells from fresh biopsy/surgical samples for up to three days prior to analysis of phenotypic characteristics. Results: We show that this test distinguishes live normal and tumor cells via molecular and biophysical biomarkers. The primary biomarkers are calculated using objective machine vision algorithms and are used to derive secondary metrics termed “Metastatic Potential (MP) and Oncogenic Potential (OP)”. In comparing clinical measures with results of this test, concordance analysis show that OP and MP are statistically significant in distinguishing between Gleason 6 and Gleason 7 with 85% sensitivity and 80% specificity. Conclusions: This phenotypic diagnostic generates scoring metrics of MP and OP that correlate with 1) aggressive vs. indolent Gleason 6, 2) seminal vesicle invasion, 3) occurrence of margins after RP, 4) lymph node invasion and 5) systemic metastatic process. These results will further help stratify patient tumors to improve clinical decision-making in low to intermediate- and high-risk prostate cancer populations, and potentially avoid unnecessary surgery or radiation, ultimately leading to improved patient quality of life.

scholarly journals Fractal circuit sensors enable rapid quantification of biomarkers for donor lung assessment for transplantation

2015 ◽  
Vol 1 (7) ◽  
pp. e1500417 ◽  
Author(s):  
Andrew T. Sage ◽  
Justin D. Besant ◽  
Laili Mahmoudian ◽  
Mahla Poudineh ◽  
Xiaohui Bai ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Three Dimensional ◽  
Extended Period ◽  
Clinical Decision ◽  
Gene Profiling ◽  
Assessment Process ◽  
Human Donor ◽  
Sensitive Organ ◽  
Donor Lung ◽  
Lung Biopsies

Biomarker profiling is being rapidly incorporated in many areas of modern medical practice to improve the precision of clinical decision-making. This potential improvement, however, has not been transferred to the practice of organ assessment and transplantation because previously developed gene-profiling techniques require an extended period of time to perform, making them unsuitable in the time-sensitive organ assessment process. We sought to develop a novel class of chip-based sensors that would enable rapid analysis of tissue levels of preimplantation mRNA markers that correlate with the development of primary graft dysfunction (PGD) in recipients after transplant. Using fractal circuit sensors (FraCS), three-dimensional metal structures with large surface areas, we were able to rapidly (<20 min) and reproducibly quantify small differences in the expression of interleukin-6 (IL-6), IL-10, and ATP11B mRNA in donor lung biopsies. A proof-of-concept study using 52 human donor lungs was performed to develop a model that was used to predict, with excellent sensitivity (74%) and specificity (91%), the incidence of PGD for a donor lung. Thus, the FraCS-based approach delivers a key predictive value test that could be applied to enhance transplant patient outcomes. This work provides an important step toward bringing rapid diagnostic mRNA profiling to clinical application in lung transplantation.

scholarly journals The Role of Chemokines in the Development of Gastric Cancer—Diagnostic and Therapeutic Implications

2020 ◽  
Vol 21 (22) ◽  
pp. 8456
Author(s):  
Elzbieta Pawluczuk ◽  
Marta Łukaszewicz-Zając ◽  
Barbara Mroczko
Keyword(s):  
Gastric Cancer ◽  
Clinical Decision Making ◽  
Current Knowledge ◽  
Cell Communication ◽  
Clinical Decision ◽  
Late Presentation ◽  
Therapeutic Implications ◽  
Small Proteins ◽  
Novel Biomarkers ◽  
Specific Receptors

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC.

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