RANK-Fc: A therapeutic antagonist for RANK-L in myeloma

Abstract

Steady flows of gas and particles in unbounded‐fluidized beds have been shown to lose stability to localized voidage disturbances. An insight is provided into the linear stability of bounded gas‐particle flows using a kinetic theory approach. The stability analysis is carried out for two illustrative sets corresponding to fluidized systems having walls acting as sinks and sources of fluctuation energy. Instabilities are characterized by computing leading eigenvalue profiles and dominant eigenfunction contour maps. Results show two types of dominant instability patterns (symmetric and antisymmetric) for flow in a vertical duct, both of which propagate through the bed in the form of traveling waves at speeds comparable to that of the solid phase. Moreover, model predictions show that increasing solids fraction and decreasing particle inelasticity will suppress the wavy disturbance. The physical mechanism of instability formation is further investigated using a term‐by‐term method of analysis. Results show that instability modes can be suppressed if solid phase inertia or inelastic particle collisions are eliminated from the momentum and pseudo‐thermal energy balance equations. Finally, the symmetric instabilities were shown to develop into bubble‐like structures while the antisymmetric instabilities develop into streamer‐like structures. © 2007 American Institute of Chemical Engineers AIChE J, 2007

A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer

“…7,14,28,29 In patients with myeloma and breast cancerrelated bone metastases, bone resorption was reduced by recombinant OPG treatment, an effect that was comparable to a single injection of a bisphosphonate. 30 Recombinant OPG when administered systemically has a half-life of several days, thus to obtain a clinically significant response would require multiple injections over a period of time.…”

Receptor Activator of NF-κB (RANK) Ligand Induces Ectodomain Shedding of RANK in Murine RAW264.7 Macrophages

“…For example, it is well established that cleaved TNFR1 and TNFR2 are capable of binding to TNF-a and suppressing TNF-a-TNFR signaling and that dysregulation of the shedding of these receptors results in aberrant immunoreactions (30)(31)(32). Similarly, recombinant soluble RANK (Glu 30 -Pro 213 ) and RANK-Fc were demonstrated to inhibit RANKLinduced osteoclastogenesis in vitro and to prevent the formation of metastatic bone lesions in xenograft tumor models (33)(34)(35)(36). We also generated soluble RANK composed of the extracellular domain N terminus to the putative cleavage sites and observed a similar inhibitory effect on RANKL-induced osteoclastogenesis in vitro.…”

Homing of Cancer Cells to the Bone

“…Soluble RANKL released from prostate cancer cells by MMP-7 is also thought to have a role in establishment of prostate cancer bone metastases and osteolysis associated with prostate cancer bone lesions [132]. In a SCID mouse model of multiple myeloma tumor RANKL inhibition with recombinant RANK-Fc protein not only reduces multiple myeloma induced osteolysis, but also causes a marked decline in tumor burden, as measured by serum protein levels and histology [133]. RANKL triggers migration of human epithelial cancer cells and melanoma cells that express the receptor RANK.…”