ABSTRACT
The Epstein-Barr virus (EBV) is associated with various tumor types, including nasopharyngeal carcinoma and lymphoproliferative disorders. While much is known about EBV-related epithelial and lymphoid tumors, there is a paucity of knowledge concerning EBV-associated mesenchymal tumors. This review aims to provide a comprehensive overview of EBV-associated mesenchymal tumors, encompassing their clinical features, pathological characteristics, pathophysiology, prognostic factors, and current treatment approaches. Through an extensive literature search using the PubMed database, we were able to identify three distinct EBV-associated mesenchymal tumors: EBV-associated smooth muscle tumors, inflammatory pseudotumor-like follicular dendritic cell sarcomas, and EBV-associated osteosarcomas. Although this review extensively explored the different aspects of these mesenchymal tumors, our comprehension of the underlying pathophysiology in this context is still incomplete. Therefore, we hope that this review paper will not only serve as a valuable repository of information but also serve as a catalyst for prospective in vitro and in vivo research studies to bridge the existing knowledge gap surrounding pathophysiology, ultimately making an important contribution to shaping future therapeutic approaches.
ABSTRACT
Relapse-prone, poor prognosis neuroblastoma is frequently characterized by deletion of chr1p36 where tumor suppressor gene KIF1Bß resides. Interestingly, many 1p36-positive patients failed to express KIF1Bß protein. Since altered cellular redox status has been reported to be involved in cell death and protein modification, we investigated the relationship between reactive oxygen species (ROS) and KIF1Bß. Here, we showed that wild-type KIF1Bß protein expression positively correlates with superoxide (O2-) and total ROS levels in neuroblastoma cells, unlike apoptotic loss-of-function KIF1Bß mutants. Overexpression of KIF1Bß apoptotic domain variants increases total ROS and, specifically O2-, whereas knockdown of endogenous KIF1Bß decreases ROS and O2-. Interestingly, O2- increases KIF1Bß protein expression, independent of the proteasomal degradation pathway. Scavenging O2- or ROS decreases KIF1Bß protein expression and subsequent apoptosis. Moreover, treatment with investigational redox compound Gliotoxin increases O2-, KIF1Bß protein expression, apoptosis and colony formation inhibition. Overall, our findings suggest that ROS and O2- may be important downstream effectors of KIF1Bß-mediated apoptosis. Subsequently, O2- produced may increase KIF1Bß protein expression in a positive feedback mechanism. Therefore, ROS and, specifically O2-, may be critical regulators of KIF1Bß-mediated apoptosis and its protein expression in neuroblastoma.
