scholarly journals Therapeutic Targets and Signaling Pathways for Diagnosis of Myeloma

2019 ◽  
Author(s):  
Zeeshan Ansar Ahmed ◽  
Ashgar Nasir ◽  
Muhammad Shariq Shaikh ◽  
Tariq Moatter ◽  
Afshan Asghar Rasheed
Keyword(s):  
Signaling Pathways ◽  
Therapeutic Targets

Inositide-dependent signaling pathways as new therapeutic targets in myelodysplastic syndromes

2015 ◽  
Vol 20 (6) ◽  
pp. 677-687 ◽  
Author(s):  
Sara Mongiorgi ◽  
Carlo Finelli ◽  
Yong Ryoul Yang ◽  
Cristina Clissa ◽  
James A. McCubrey ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Myelodysplastic Syndromes ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Receptor Crosstalk ◽  
Overt Proteinuria

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.

scholarly journals Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaobo Zhu ◽  
Yau Tsz Chan ◽  
Patrick S. H. Yung ◽  
Rocky S. Tuan ◽  
Yangzi Jiang
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Bone Remodeling ◽  
Molecular Mechanism ◽  
Subchondral Bone ◽  
Therapeutic Target ◽  
Therapeutic Targets ◽  
Regenerative Therapies

There is emerging awareness that subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). This review presents recent investigations on the cellular and molecular mechanism of subchondral bone remodeling, and summarizes the current interventions and potential therapeutic targets related to OA subchondral bone remodeling. The first part of this review covers key cells and molecular mediators involved in subchondral bone remodeling (osteoclasts, osteoblasts, osteocytes, bone extracellular matrix, vascularization, nerve innervation, and related signaling pathways). The second part of this review describes candidate treatments for OA subchondral bone remodeling, including the use of bone-acting reagents and the application of regenerative therapies. Currently available clinical OA therapies and known responses in subchondral bone remodeling are summarized as a basis for the investigation of potential therapeutic mediators.

scholarly journals Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer

2014 ◽  
Vol 66 (4) ◽  
pp. 1033-1079 ◽  
Author(s):  
Ronald C. Bruntz ◽  
Craig W. Lindsley ◽  
H. Alex Brown
Keyword(s):  
Phosphatidic Acid ◽  
Signaling Pathways ◽  
Phospholipase D ◽  
Therapeutic Targets

scholarly journals Genome‐wide transcriptomic and proteomic studies of Rett syndrome mouse models identify common signaling pathways and cellular functions as potential therapeutic targets

2019 ◽  
Vol 40 (12) ◽  
pp. 2184-2196 ◽  
Author(s):  
Rahul Krishnaraj ◽  
Florencia Haase ◽  
Bronte Coorey ◽  
Edward J Luca ◽  
Ingar Wong ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Rett Syndrome ◽  
Mouse Models ◽  
Therapeutic Targets ◽  
Cellular Functions ◽  
Genome Wide

scholarly journals Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets

Leukemia ◽  
2020 ◽  
Author(s):  
Shady Adnan-Awad ◽  
Daehong Kim ◽  
Helena Hohtari ◽  
Komal Kumar Javarappa ◽  
Tania Brandstoetter ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Drug Sensitivity ◽  
Lymphoblastic Leukemia ◽  
High Risk Patient ◽  
Therapeutic Targets ◽  
Hematopoietic Progenitor Cell ◽  
Sensitivity Testing

Abstract The oncogenic protein Bcr-Abl has two major isoforms, p190Bcr-Abl and p210Bcr-Abl. While p210Bcr-Abl is the hallmark of chronic myeloid leukemia (CML), p190Bcr-Abl occurs in the majority of Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients. In CML, p190Bcr-Abl occurs in a minority of patients associating with distinct hematological features and inferior outcomes, yet the pathogenic role of p190Bcr-Abl and potential targeting therapies are largely uncharacterized. We employed next generation sequencing, phospho-proteomic profiling, and drug sensitivity testing to characterize p190Bcr-Abl in CML and hematopoietic progenitor cell line models (Ba/f3 and HPC-LSK). p190Bcr-Abl CML patients demonstrated poor response to imatinib and frequent mutations in epigenetic modifiers genes. In contrast with p210Bcr-Abl, p190Bcr-Abl exhibited specific transcriptional upregulation of interferon, interleukin-1 receptor, and P53 signaling pathways, associated with hyperphosphorylation of relevant signaling molecules including JAK1/STAT1 and PAK1 in addition to Src hyperphosphorylation. Comparable to p190Bcr-Abl CML patients, p190Bcr-Abl cell lines demonstrated similar transcriptional and phospho-signaling signatures. With the drug sensitivity screening we identified targeted drugs with specific activity in p190Bcr-Abl cell lines including IAP-, PAK1-, and Src inhibitors and glucocorticoids. Our results provide novel insights into the mechanisms underlying the distinct features of p190Bcr-Abl CML and promising therapeutic targets for this high-risk patient group.

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