Rabbit Anti-Human MMP15 (Cleaved-Tyr132) polyclonal antibody

Endometrial cancer is the most frequent gynecologic cancer in women. Long-term outcomes for: patients with advanced stage or recurrent disease are poor. Targeted molecular therapy against the vascular endothelial growth factor (VEGF) and its receptors constitute a new therapeutic option for these patients. The goal of our study was to assess the potential effectiveness of inhibition of VEGF/VEGFR signaling in a xenograft model of endometrial cancer using bevacizumab (Avastin, a humanized antibody against VEGFA). We also aimed to identify molecular markers of sensitivity or resistance to this agent. We show that bevacizumab retards tumor growth in athymic mice by inhibiting molecular components of signaling pathways that sustain cell survival and proliferation. We also demonstrate that resistance to bevacizumab may involve up-regulation of anti-apoptotic genes and certain proto-oncogenes. We propose that down-regulation of ARHGAP6 and MMP15 transcripts indicates that tumors are sensitive to bevacizumab whereas inhibition of PKC delta- or S6K-dependent signaling and up-regulation of TNFRS4 or MMP13 and MMP14 mark a developing resistance to bevacizumab therapy. Interestingly, the significant activation of c-Jun oncogene detected in bevacizumab-treated tumors suggests that, in endometrial cancers, the c-Jun-mediated pathway(s) contribute to bevacizumab resistance.

Mayaro virus (MAYV) is an emerging arthritogenic alphavirus belonging to the Togaviridae family. Infection leads to a dengue-like illness accompanied by severe polyarthralgia. However, the molecular and cellular mechanisms of arthritis as a result of MAYV infection remain poorly understood. In the present study, we assess the susceptibility of human chondrocytes (HC), fibroblast-like synoviocytes and osteoblasts that are the major cell types involved in osteoarthritis, to infection with MAYV. We show that these cells are highly permissive to MAYV infection and that viral RNA copy number and viral titers increase over time in infected cells. Knowing that HC are the primary cells in articular cartilage and are essential for maintaining the cartilaginous matrix, gene expression studies were conducted in MAYV-infected primary HC using polymerase chain reaction (PCR) arrays. The infection of the latter cells resulted in an induction in the expression of several matrix metalloproteinases (MMP) including MMP1, MMP7, MMP8, MMP10, MMP13, MMP14 and MMP15 which could be involved in the destruction of articular cartilage. Infected HC were also found to express significantly increased levels of various IFN-stimulated genes and arthritogenic mediators such as TNF-alpha and IL-6. In conclusion, MAYV-infected primary HC overexpress arthritis-related genes, which may contribute to joint degradation and pathogenesis.