scholarly journals Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities

2019 ◽  
Vol 3 (21) ◽  
pp. 3307-3321 ◽  
Author(s):  
Sophie Cardin ◽  
Mélanie Bilodeau ◽  
Mathieu Roussy ◽  
Léo Aubert ◽  
Thomas Milan ◽  
...  
Keyword(s):  
Pediatric Leukemia ◽  
Disease Biomarkers ◽  
Human Models ◽  
Key Points ◽  
New Biomarkers ◽  
Pharmacologic Inhibition

Key PointsEngineered human models of high-fatality pediatric leukemia are relevant to uncover disease biomarkers and therapeutic vulnerabilities. NUP98-KDM5A–associated AMKL expresses SELP, MPIG6B, and NEO1 biomarkers and is sensitive to pharmacologic inhibition with ruxolitinib.

scholarly journals MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia

Blood ◽  
2015 ◽  
Vol 126 (19) ◽  
pp. 2202-2212 ◽  
Author(s):  
Courtney L. Jones ◽  
Christy M. Gearheart ◽  
Susan Fosmire ◽  
Cristina Delgado-Martin ◽  
Nikki A. Evensen ◽  
...  
Keyword(s):  
Cell Death ◽  
Resistance Mechanisms ◽  
Mapk Signaling ◽  
Glucocorticoid Resistance ◽  
Signaling Cascades ◽  
Pediatric Leukemia ◽  
Mek Inhibition ◽  
Key Points ◽  
Pharmacologic Inhibition

Key Points Genetic or pharmacologic inhibition of MEK4 and MEK2 enhances prednisolone-induced cell death in ALL models. MAPK signaling cascades are activated at relapse compared to diagnosis in ALL samples and have enhanced response to MEK inhibition.

scholarly journals miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. e21-e32 ◽  
Author(s):  
Ruggiero Norfo ◽  
Roberta Zini ◽  
Valentina Pennucci ◽  
Elisa Bianchi ◽  
Simona Salati ◽  
...  
Keyword(s):  
Expression Analysis ◽  
Mirna Expression ◽  
Therapeutic Targets ◽  
Primary Myelofibrosis ◽  
Integrative Analysis ◽  
Cd34 Cells ◽  
Key Points ◽  
Differential Gene ◽  
New Biomarkers

Key Points Differential gene and miRNA expression analysis in PMF granulocytes identifies new biomarkers and putative therapeutic targets. Activation of the miR-155/JARID2 axis in PMF CD34+ cells results in overproduction of MK precursors.

scholarly journals Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells

Blood ◽  
2016 ◽  
Vol 128 (8) ◽  
pp. 1063-1075 ◽  
Author(s):  
Douaa Dhahri ◽  
Kaori Sato-Kusubata ◽  
Makiko Ohki-Koizumi ◽  
Chiemi Nishida ◽  
Yoshihiko Tashiro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Key Points ◽  
Pharmacologic Inhibition

Key Points tPA expands mesenchymal stromal cells (MSCs) in the bone marrow by a cytokine (KitL and PDGF-BB) crosstalk with endothelial cells. Pharmacologic inhibition of receptor tyrosine kinases (c-Kit and PDGFRα) impairs tPA-mediated MSC proliferation.

scholarly journals D-Amino Acids and D-Amino Acid-Containing Peptides: Potential Disease Biomarkers and Therapeutic Targets?

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1716
Author(s):  
Mohamed Abdulbagi ◽  
Liya Wang ◽  
Orwa Siddig ◽  
Bin Di ◽  
Bo Li
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Analytical Techniques ◽  
The Other ◽  
Disease Development ◽  
Disease Biomarkers ◽  
New Biomarkers ◽  
Structure Of Proteins

In nature, amino acids are found in two forms, L and D enantiomers, except for glycine which does not have a chiral center. The change of one form to the other will lead to a change in the primary structure of proteins and hence may affect the function and biological activity of proteins. Indeed, several D-amino acid-containing peptides (DAACPs) were isolated from patients with cataracts, Alzheimer’s and other diseases. Additionally, significant levels of free D-amino acids were found in several diseases, reflecting the disease conditions. Studying the molecular mechanisms of the DAACPs formation and the alteration in D-amino acids metabolism will certainly assist in understanding these diseases and finding new biomarkers and drug targets. In this review, the presence of DAACPs and free D-amino acids and their links with disease development and progress are summarized. Similarly, we highlight some recent advances in analytical techniques that led to improvement in the discovery and analysis of DAACPs and D-amino acids.

Biomarkers for Diagnosing and Staging of Fabry Disease

2018 ◽  
Vol 25 (13) ◽  
pp. 1530-1537 ◽  
Author(s):  
Johannes Kramer ◽  
Frank Weidemann
Keyword(s):  
Fabry Disease ◽  
Clinical Relevance ◽  
Cardiac Involvement ◽  
Lysosomal Storage ◽  
Timely Initiation ◽  
Disease Biomarkers ◽  
Long Time ◽  
New Biomarkers ◽  
Deficient Activity

Background: Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of α -galactosidase A which leads to progressive intracellular accumulation of globotriaosylceramide in tissues and organs including heart, kidney, vascular endothelium, the nervous system, the eyes and the skin. Cardiac involvement is common, leads to fatal complications and is mainly responsible for reduced life expectancy in Fabry disease. The exact staging of disease progression and timely initiation of treatment is essential in Fabry disease. Therefore, it is essential to use the possibilities of specific biomarkers for early detection of organ involvement or early diagnosis. Methods: By the use of Pubmed all relevant papers for biomarkers in Fabry disease were screened. The quality of retrieved papers was appraised using standard tools. Finally, 70 peer reviewed paper were included. Results: In the past biomarkers for Fabry disease biomarkers did not have clinical relevance. Nowadays, a lot of research is focusing on identification of new biomarkers and their clinical relevance. Only two biomarkers reached clinical applicability. Lyso-GB3 for identification of atypical FD variants and hsTNT for identification of cardiac involvement, which should indicate further diagnostics. Treatment response to ERT can be monitored by lyso-GB3 but data for long-time outcome are missing. A lot of GB3-related analogs are identified in urine and plasma, some of which might play an important role for managing Fabry disease in future. Conclusion: In conclusion, we suggest to measure lyso-GB3 and hsTNT at least once a year. The routine measurement of these two biomarkers will help now for the staging of every individual patient and in addition, will help for a better general understanding of Fabry disease.

scholarly journals Pharmacologic Inhibition of β-Catenin With Pyrvinium Inhibits Murine and Human Models of Wilms Tumor

2017 ◽  
Vol 25 (9) ◽  
pp. 1653-1664 ◽  
Author(s):  
Dina Polosukhina ◽  
Harold D. Love ◽  
Harold L. Moses ◽  
Ethan Lee ◽  
Roy Zent ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Human Models ◽  
Pharmacologic Inhibition

scholarly journals IκB kinase phosphorylation of SNAP-23 controls platelet secretion

Blood ◽  
2013 ◽  
Vol 121 (22) ◽  
pp. 4567-4574 ◽  
Author(s):  
Zubair A. Karim ◽  
Jinchao Zhang ◽  
Meenakshi Banerjee ◽  
Michael C. Chicka ◽  
Rania Al Hawas ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Fusion ◽  
Iκb Kinase ◽  
Key Points ◽  
Kinase Phosphorylation ◽  
Pharmacologic Inhibition ◽  
Platelet Secretion

Key Points Nongenomic role for IκB kinase in platelet secretion: IKK phosphorylates SNAP-23, which affects granule-plasma membrane fusion. Pharmacologic inhibition or deletion of platelet IKK affects bleeding times.

scholarly journals Platelet 12-LOX is essential for FcγRIIa-mediated platelet activation

Blood ◽  
2014 ◽  
Vol 124 (14) ◽  
pp. 2271-2279 ◽  
Author(s):  
Jennifer Yeung ◽  
Benjamin E. Tourdot ◽  
Pilar Fernandez-Perez ◽  
Joanne Vesci ◽  
Jin Ren ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Therapeutic Target ◽  
Therapeutic Approach ◽  
Genetic Ablation ◽  
Immune Mediated ◽  
Key Points ◽  
Human And Mouse ◽  
Pharmacologic Inhibition ◽  
Novel Therapeutic

Key PointsPlatelet 12-LOX modulates FcγRIIa signaling and presents a viable therapeutic target in the prevention of immune-mediated thrombosis. This novel therapeutic approach is supported by pharmacologic inhibition and genetic ablation of 12-LOX in human and mouse platelets.

scholarly journals PTAFR Exaggerates Microglia-Mediated Microenvironment via IL10-STAT3 Signaling: A Novel Perspective on Potential Biomarker and Target for AD Diagnosis and Treatment

2021 ◽  
Author(s):  
Junxiu Liu ◽  
Linchi Jiao ◽  
Xin Zhong ◽  
Weifan Yao ◽  
Ke Du ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Huperzine A ◽  
Diagnosis And Treatment ◽  
Stat3 Signaling ◽  
Potential Biomarker ◽  
Key Points ◽  
Highly Expressed Genes ◽  
Novel Strategy ◽  
New Biomarkers ◽  
The Brain

Abstract Background: Early diagnosis and effective intervention become the key points for delaying Alzheimer’s progression. Therefore, we aim to find new biomarkers for early diagnosis of Alzheimer (AD) by bioinformatics, and to reveal the possible mechanisms. Methods and results: GSE1297, GSE63063, and GSE110226 in the GEO database were used to screen out the differentially highly expressed genes. We found out a potential biomarker PTAFR differentially highly expressed in the brain tissue, peripheral blood and cerebrospinal fluid of AD patients. Furthermore, we found higher PTAFR level in the plasma and brain tissues of APP/PS1 mice. Simultaneously, it was uncovered that PTAFR mediated the inflammatory response to exaggerate microenvironment specially mediated by microglia through the IL10-STAT3 pathway. In addition, we also found PTAFR was a possible target for some anti-AD compounds such as EGCG, donepezil, curcumin, memantine, and Huperzine A.Conclusions: PTAFR was a potential biomarker for early AD diagnosis and treatment correlated with microglia-mediated microenvironment, and an important possible target to make novel strategy for clinical treatment and new drug discovery in AD.

scholarly journals The miRNA Expression Profile of Experimental Autoimmune Encephalomyelitis Reveals Novel Potential Disease Biomarkers

2018 ◽  
Vol 19 (12) ◽  
pp. 3990 ◽  
Author(s):  
Shivaprasad Venkatesha ◽  
Steven Dudics ◽  
Yang Song ◽  
Anup Mahurkar ◽  
Kamal Moudgil
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Bioinformatics Analysis ◽  
Inverse Correlation ◽  
Serum Levels ◽  
Mirna Expression Profile ◽  
Autoimmune Encephalomyelitis ◽  
Mirna Microarray ◽  
Disease Biomarkers ◽  
New Biomarkers ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a debilitating autoimmune disease affecting over 2.3 million people worldwide, and it is characterized by inflammation and demyelination of nerve cells. The currently available biomarkers for the diagnosis and management of MS have inherent limitations, therefore, additional new biomarkers are needed. We studied the microRNA (miRNA) profile of splenocytes of mice having experimental autoimmune encephalomyelitis (EAE), a model of human MS. A miRNA-microarray analysis revealed increased expression of nine miRNAs (let-7e, miR-23b, miR-31, miR-99b, miR-125a, miR-146b, miR-155, miR-193b, and miR-221) following EAE development. Interestingly, serum levels of miR-99b, miR-125a, and miR-146b were significantly higher in EAE mice compared to normal mice. Bioinformatics analysis revealed the experimentally validated as well as predicted gene targets of specific miRNAs that are important for disease progression in MS. Specifically, we observed inverse correlation in the levels of miR-99b versus LIF, and between miR-125a versus BDNF and LIF. Our results suggest that above-mentioned miRNAs may play a crucial role in the pathogenesis of MS, and that miR-99b, miR-125a, and miR-146b in particular may serve as useful biomarkers for disease activity.

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