scholarly journals Cell-free microRNAs as Non-invasive Diagnostic and Prognostic Biomarkers in Pancreatic Cancer

2020 ◽  
Vol 20 (8) ◽  
pp. 569-580
Author(s):  
Natalia A. Gablo ◽  
Vladimir Prochazka ◽  
Zdenek Kala ◽  
Ondrej Slaby ◽  
Igor Kiss
Keyword(s):  
Pancreatic Cancer ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Prediction Of Response ◽  
Non Invasive ◽  
Current Trends ◽  
Diagnostic Management ◽  
Prognosis And Prediction ◽  
Multimodal Management ◽  
Biomarker Research

Pancreatic cancer (PaC) is one of the most lethal cancers, with an increasing global incidence rate. Unfavorable prognosis largely results from associated difficulties in early diagnosis and the absence of prognostic and predictive biomarkers that would enable an individualized therapeutic approach. In fact, PaC prognosis has not improved for years, even though much efforts and resources have been devoted to PaC research, and the multimodal management of PaC patients has been used in clinical practice. It is thus imperative to develop optimal biomarkers, which would increase diagnostic precision and improve the post-diagnostic management of PaC patients. Current trends in biomarker research envisage the unique opportunity of cell-free microRNAs (miRNAs) present in circulation to become a convenient, non-invasive tool for accurate diagnosis, prognosis and prediction of response to treatment. This review analyzes studies focused on cell-free miRNAs in PaC. The studies provide solid evidence that miRNAs are detectable in serum, blood plasma, saliva, urine, and stool, and that they present easy-to-acquire biomarkers with strong diagnostic, prognostic and predictive potential.

scholarly journals Recent Advances in the Discovery of Biomarkers for Canine Osteosarcoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Anita K. Luu ◽  
Geoffrey A. Wood ◽  
Alicia M. Viloria-Petit
Keyword(s):  
Clinical Practice ◽  
Standard Treatment ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Future Directions ◽  
Diagnostic Biomarkers ◽  
Canine Osteosarcoma ◽  
The Past ◽  
Biomarker Research

Canine osteosarcoma (OSA) is an aggressive malignancy that frequently metastasizes to the lung and bone. Not only has there been essentially no improvement in therapeutic outcome over the past 3 decades, but there is also a lack of reliable biomarkers in clinical practice. This makes it difficult to discriminate which patients will most benefit from the standard treatment of amputation and adjuvant chemotherapy. The development of reliable diagnostic biomarkers could aid in the clinical diagnosis of primary OSA and metastasis; while prognostic, and predictive biomarkers could allow clinicians to stratify patients to predict response to treatment and outcome. This review summarizes biomarkers that have been explored in canine OSA to date. The focus is on molecular biomarkers identified in tumor samples as well as emerging biomarkers that have been identified in blood-based (liquid) biopsies, including circulating tumor cells, microRNAs, and extracellular vesicles. Lastly, we propose future directions in biomarker research to ensure they can be incorporated into a clinical setting.

scholarly journals Circulating biomarkers in malignant pleural mesothelioma

2020 ◽  
Vol 1 (6) ◽  
Author(s):  
Giuseppe Viscardi ◽  
Davide Di Natale ◽  
Morena Fasano ◽  
Marta Brambilla ◽  
Riccardo Lobefaro ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Pleural Mesothelioma ◽  
Precision Oncology ◽  
Advanced Stage ◽  
Circulating Biomarkers ◽  
Prediction Of Response ◽  
Non Invasive ◽  
Prognosis And Prediction ◽  
Aggressive Tumor

Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

The role of microRNAs in gliomas – Therapeutic implications

2020 ◽  
Vol 13 ◽  
Author(s):  
Theodora Katsila ◽  
Dimitrios Kardamakis
Keyword(s):  
Complex Disease ◽  
Malignant Gliomas ◽  
Kappa Statistic ◽  
Individual Variability ◽  
Response To Treatment ◽  
Disease Phenotype ◽  
Therapeutic Implications ◽  
Non Invasive ◽  
Gene Environment ◽  
Sas Macro

Background: Malignant gliomas constitute a complex disease phenotype that demands optimum decisionmaking. Despite being the most common type of primary brain tumors, gliomas are highly heterogeneous when their pathophysiology and response to treatment are considered. Such inter-individual variability also renders differential and early diagnosis extremely difficult. Recent evidence highlight that the gene-environment interplay becomes of fundamental importance in oncogenesis and progression of gliomas. Objective: To unmask key features of the gliomas disease phenotype and map the inter-individual variability of patients, we explore genotype-to-phenotype associations. Emphasis is put on microRNAs as they regulate gene expression, have been implicated in the pathogenesis of gliomas and may serve as theranostics, empowering non-invasive strategies (circulating free or in exosomes). Method: We mined text and omic datasets (as of 2019) and conducted a mixed-method content analysis. A novel framework was developed to meet the aims of our analysis, interrogating data in terms of content and context. We relied on literature data from PubMed/Medline and Scopus, as they are considered the largest abstract and citation databases of peer-reviewed literature. To avoid selection biases, both publicly available and private texts have been assessed. Both percent agreement and Cohen's kappa statistic have been calculated to avoid biases by SAS macro MAGREE with multicategorical ratings. Results: Gliomas serve as a paradigm for multifaceted datasets, despite data sparsity and scarcity. miRNAs and miRNAbased therapeutics are ready for prime time. Exosomal miRNAs empower non-invasive strategies, surpassing circulating free miRNAs, when accuracy and precision are considered. Conclusion: miRNAs holds promise as theranostics.

scholarly journals Evaluating the Possibility of Translating Technological Advances in Non-Invasive Continuous Lactate Monitoring into Critical Care

Sensors ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 879
Author(s):  
Robert D. Crapnell ◽  
Ascanio Tridente ◽  
Craig E. Banks ◽  
Nina C. Dempsey-Hibbert
Keyword(s):  
Critical Care ◽  
Continuous Monitoring ◽  
Performance Monitoring ◽  
Plasma Concentrations ◽  
Lactate Production ◽  
Anaerobic Exercise ◽  
Response To Treatment ◽  
Diverse Range ◽  
Non Invasive ◽  
Technological Advances

Lactate is widely measured in critically ill patients as a robust indicator of patient deterioration and response to treatment. Plasma concentrations represent a balance between lactate production and clearance. Analysis has typically been performed with the aim of detecting tissue hypoxia. However, there is a diverse range of processes unrelated to increased anaerobic metabolism that result in the accumulation of lactate, complicating clinical interpretation. Further, lactate levels can change rapidly over short spaces of time, and even subtle changes can reflect a profound change in the patient’s condition. Hence, there is a significant need for frequent lactate monitoring in critical care. Lactate monitoring is commonplace in sports performance monitoring, given the elevation of lactate during anaerobic exercise. The desire to continuously monitor lactate in athletes has led to the development of various technological approaches for non-invasive, continuous lactate measurements. This review aims firstly to reflect on the potential benefits of non-invasive continuous monitoring technology within the critical care setting. Secondly, we review the current devices used to measure lactate non-invasively outside of this setting and consider the challenges that must be overcome to allow for the translation of this technology into intensive care medicine. This review will be of interest to those developing continuous monitoring sensors, opening up a new field of research.

scholarly journals Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3481
Author(s):  
Kendelle J. Murphy ◽  
Cecilia R. Chambers ◽  
David Herrmann ◽  
Paul Timpson ◽  
Brooke A. Pereira
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Development ◽  
Treatment Resistance ◽  
Tumor Stroma ◽  
Response To Treatment ◽  
Ductal Adenocarcinoma ◽  
Cell Phenotype ◽  
Stromal Compartment ◽  
Clinical Prognosis ◽  
Functional Value

Many cancer studies now recognize that disease initiation, progression, and response to treatment are strongly influenced by the microenvironmental niche. Widespread desmoplasia, or fibrosis, is fundamental to pancreatic cancer development, growth, metastasis, and treatment resistance. This fibrotic landscape is largely regulated by cancer-associated fibroblasts (CAFs), which deposit and remodel extracellular matrix (ECM) in the tumor microenvironment (TME). This review will explore the prognostic and functional value of the stromal compartment in predicting outcomes and clinical prognosis in pancreatic ductal adenocarcinoma (PDAC). We will also discuss the major dynamic stromal alterations that occur in the pancreatic TME during tumor development and progression, and how the stromal ECM can influence cancer cell phenotype, metabolism, and immune response from a biochemical and biomechanical viewpoint. Lastly, we will provide an outlook on the latest clinical advances in the field of anti-fibrotic co-targeting in combination with chemotherapy or immunotherapy in PDAC, providing insight into the current challenges in treating this highly aggressive, fibrotic malignancy.

scholarly journals Changes in Neutrophil–Lymphocyte or Platelet–Lymphocyte Ratios and Their Associations with Clinical Outcomes in Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 10 (7) ◽  
pp. 1427
Author(s):  
Steven D. Nathan ◽  
Jayesh Mehta ◽  
John Stauffer ◽  
Elizabeth Morgenthien ◽  
Ming Yang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Clinical Outcomes ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Response To Treatment ◽  
Reference Ranges ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
The Relationship

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in IPF, and the relationship between NLR or PLR changes and clinical outcomes over 12 months. This post hoc analysis included patients with IPF from the Phase III, double-blind trials of pirfenidone, ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729). The relationship between change from baseline to Month 12 in NLR or PLR (divided into quartiles (Q1–Q4)) and outcomes (mortality, respiratory hospitalization, declines in lung function, exercise capacity and quality of life) was assessed. Estimated reference ranges at baseline for all patients analyzed (n = 1334) were 1.1–6.4 for NLR and 56.8–250.5 for PLR. Significant trends were observed across NLR and PLR quartiles for all outcomes in placebo-treated patients, with patients manifesting the greatest NLR or PLR changes experiencing the worst outcomes. These results suggest that the greatest NLR or PLR changes over 12 months were associated with worse clinical outcomes. Further research is needed to determine the utility of NLR and PLR as prognostic biomarkers in IPF.

scholarly journals Clinical Perspective on Proteomic and Glycomic Biomarkers for Diagnosis, Prognosis, and Prediction of Pancreatic Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2655
Author(s):  
Randa G. Hanna-Sawires ◽  
Jorinde H. Schiphuis ◽  
Manfred Wuhrer ◽  
Hans F. A. Vasen ◽  
Monique E. van Leerdam ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Techniques ◽  
Protein Glycosylation ◽  
Ductal Adenocarcinoma ◽  
Careful Study ◽  
Prognosis And Prediction ◽  
Prognostic Stratification ◽  
Neo Adjuvant Chemotherapy ◽  
New Biomarkers ◽  
Study Designs

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.

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