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The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

NF κB and Kidney Injury
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

PDZ Binding Kinase (PBK) - a Novel Gene Driving Genomic Evolution in Multiple Myeloma
As in all cancers, genomic instability leads to ongoing acquisition of new genetic changes in multiple myeloma (MM). This adaptability underlies the development of drug resistance and progression in MM. This genomic instability is driven by cellular processes, mainly related with DNA repair and perturbed by functional changes in limited number of genes. Since kinases play a critical role in the regulation of biological processes, including DNA damage/repair signaling and are relatively easy to screen for inhibitors, we investigated for novel genes involved in the acquisition of new genomic changes in MM. Using a large geno...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kumar, S., Buon, L., Talluri, S., Shi, J., Avet-Loiseau, H., Samur, M. K., Shammas, M. A., Munshi, N. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells.
CONCLUSIONS: Our preclinical studies provide the framework for clinical evaluation of USP1 inhibitors, alone or in combination, as a potential novel MM therapy. PMID: 28270494 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - March 6, 2017 Category: Cancer & Oncology Authors: Das DS, Das A, Ray A, Song Y, Samur MK, Munshi NC, Chauhan D, Anderson KC Tags: Clin Cancer Res Source Type: research