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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

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes
Eleonora A. Braga1*†, Marina V. Fridman2†, Vitaly I. Loginov1,3, Alexey A. Dmitriev4 and Sergey G. Morozov1 1Institute of General Pathology and Pathophysiology, Moscow, Russia 2Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia 3Research Center of Medical Genetics, Moscow, Russia 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search f...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

ILK promotes angiogenic activity of mesenchymal stem cells in multiple myeloma.
Authors: Zhao W, Zhang X, Zang L, Zhao P, Chen Y, Wang X Abstract Angiogenic activity in solid tumors has been demonstrated to promote metastasis through the activation of certain proteins involved in the epithelial-mesenchymal transition-associated process. The molecular mechanism underlying multiple myeloma-induced angiogenesis involves angiogenic cytokines by plasma cells as well as their induction within the microenvironment. Integrin-linked kinase (ILK) is a highly evolutionarily conserved intracellular protein that was originally identified as an integrin-interacting protein, and extensive genetic and biochem...
Source: Oncology Letters - July 4, 2018 Category: Cancer & Oncology Tags: Oncol Lett 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

Abstract 325: Multiple myeloma in a physiologically relevant Me-HA -3D Hydrogel: Discovering new phenotypes of drug resistance
In this study we have shown that Hyaluronic acid (HA) based 3D hydrogel support human metastatic MM cancer cells survival and thus reveal new oncogenic mechanisms of drug resistant cancer stem cells.Experimental approaches: Bone marrow derived CD138 positive cells and BMSCs were isolated from MM patient samples (with IRB approval) using magnetically labeled CD138 MicroBeads (autoMACS Pro Starting Kit). Bone marrow stromal cells (BMSCs) were cultured as described by us earlier. Cell viability measurements and quantitative RT-PCR for c-myc and other related gene targets were performed using total RNA. Me-HA-3D hydrogels were...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Narayanan, B. A., Duan, B., Narayanan, N. K., Butcher, J. B., Mazumder, A. Tags: Tumor Biology Source Type: research

High throughput quantitative reverse transcription PCR assays revealing over‐expression of cancer testis antigen genes in multiple myeloma stem cell‐like side population cells
Summary Multiple myeloma (MM) stem cells, proposed to be responsible for the tumourigenesis, drug resistance and recurrence of this disease, are enriched in the cancer stem cell‐like side population (SP). Cancer testis antigens (CTA) are attractive targets for immunotherapy because they are widely expressed in cancers but only in limited types of normal tissues. We designed a high throughput assay, which allowed simultaneous relative quantifying expression of 90 CTA genes associated with MM. In the three MM cell lines tested, six CTA genes were over‐expressed in two and LUZP4 and ODF1 were universally up‐regulated in...
Source: British Journal of Haematology - May 29, 2014 Category: Hematology Authors: Jianguo Wen, Hangwen Li, Wenjing Tao, Barbara Savoldo, Jessica A. Foglesong, Lauren C. King, Youli Zu, Chung‐Che Chang Tags: Research Paper Source Type: research